chr5-177604405-C-T

Position:

chr5-177604405-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_007255.3(B4GALT7):c.277C>T(p.His93Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00224 in 1,613,858 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 10 hom. )

Consequence

B4GALT7
NM_007255.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3O:1

Conservation

PhyloP100: 7.11

Variant links:

Genes affected

B4GALT7 (HGNC:930): (beta-1,4-galactosyltransferase 7) This gene is a member of the beta-1,4-galactosyltransferase (beta4GalT) family. Family members encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose. Each beta4GalT member has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus which then remains uncleaved to function as a transmembrane anchor. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein linkage (GlcA-beta1,3-Gal-beta1,3-Gal-beta1,4-Xyl-beta1-O-Ser) found in proteoglycans. This enzyme differs from other beta4GalTs because it lacks the conserved Cys residues found in beta4GalT1-beta4GalT6 and it is located in cis-Golgi instead of trans-Golgi. Mutations in this gene have been associated with the progeroid form of Ehlers-Danlos syndrome. [provided by RefSeq, Oct 2009]

B4GALT7 links:

B4GALT7 (HGNC:):

B4GALT7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032865435).

BP6

Variant 5-177604405-C-T is Benign according to our data. Variant chr5-177604405-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 374581.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=3, not_provided=1}. Variant chr5-177604405-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00142 (217/152324) while in subpopulation NFE AF= 0.00271 (184/68016). AF 95% confidence interval is 0.00239. There are 0 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT7	NM_007255.3 linkuse as main transcript	c.277C>T	p.His93Tyr	missense_variant	2/6	ENST00000029410.10	NP_009186.1	Q9UBV7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALT7	ENST00000029410.10 linkuse as main transcript	c.277C>T	p.His93Tyr	missense_variant	2/6	1	NM_007255.3	ENSP00000029410.5		Q9UBV7

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

217

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00270

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00138

AC:

341

AN:

246966

Hom.:

AF XY:

0.00142

AC XY:

190

AN XY:

134138

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.000700

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.00232

AC:

3392

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1594

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000575

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.00290

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00142

AC:

217

AN:

152324

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00271

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00124

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00156

AC:

189

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:3Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome progeroid type

Uncertain:1Benign:1Other:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 31, 2018	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Sep 23, 2021	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32214361) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	B4GALT7: BS2 -

Ehlers-Danlos syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 27, 2021

- -

B4GALT7-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 17, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.059

T;D

Polyphen

1.0

D;.

Vest4

0.79

MVP

0.44

MPC

0.68

ClinPred

0.44

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over