18-31684372-T-A

Position:

chr18-31684372-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004775.5(B4GALT6):c.55A>T(p.Ile19Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

B4GALT6
NM_004775.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.618

Variant links:

Genes affected

B4GALT6 (HGNC:929): (beta-1,4-galactosyltransferase 6) This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes in human. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT 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 and which then remains uncleaved to function as a transmembrane anchor. This gene produces multiple protein isoforms - some of which are predicted to lack the N-terminal hydrophobic signal sequence and transmembrane domain. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. The canonical enzyme encoded by this gene is a lactosylceramide synthase important for glycolipid biosynthesis. [provided by RefSeq, Jan 2020]

B4GALT6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20027909).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT6	NM_004775.5 linkuse as main transcript	c.55A>T	p.Ile19Phe	missense_variant	1/9	ENST00000306851.10	NP_004766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALT6	ENST00000306851.10 linkuse as main transcript	c.55A>T	p.Ile19Phe	missense_variant	1/9	1	NM_004775.5	ENSP00000306459	P1	Q9UBX8-1
B4GALT6	ENST00000237019.11 linkuse as main transcript	c.55A>T	p.Ile19Phe	missense_variant	1/8	1		ENSP00000237019
B4GALT6	ENST00000383131.3 linkuse as main transcript	c.55A>T	p.Ile19Phe	missense_variant	1/8	1		ENSP00000372613		Q9UBX8-2
B4GALT6	ENST00000579372.1 linkuse as main transcript	c.-18+1358A>T		intron_variant		5		ENSP00000463961

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251316

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151704

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.55A>T (p.I19F) alteration is located in exon 1 (coding exon 1) of the B4GALT6 gene. This alteration results from a A to T substitution at nucleotide position 55, causing the isoleucine (I) at amino acid position 19 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.22

T;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.035

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.88

D;T;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0080

D;T;D

Sift4G

Uncertain

0.040

D;T;D

Polyphen

0.78

P;B;.

Vest4

0.52

MVP

0.26

MPC

1.1

ClinPred

0.18

GERP RS

3.0

Varity_R

0.39

gMVP

0.81

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