Variant chr7-7238816-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020156.5(C1GALT1):c.782T>C(p.Ile261Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000609 in 1,613,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

C1GALT1
NM_020156.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0250

Variant links:

Genes affected

C1GALT1 (HGNC:24337): (core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1) The protein encoded by this gene generates the common core 1 O-glycan structure, Gal-beta-1-3GalNAc-R, by the transfer of Gal from UDP-Gal to GalNAc-alpha-1-R. Core 1 is a precursor for many extended mucin-type O-glycans on cell surface and secreted glycoproteins. Studies in mice suggest that this gene plays a key role in thrombopoiesis and kidney homeostasis.[provided by RefSeq, Sep 2010]

C1GALT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006141424).

BP6

Variant 7-7238816-T-C is Benign according to our data. Variant chr7-7238816-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2256436.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1GALT1	NM_020156.5 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	3/4	ENST00000436587.7	NP_064541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1GALT1	ENST00000436587.7 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	3/4	5	NM_020156.5	ENSP00000389176	P1	Q9NS00-1
C1GALT1	ENST00000223122.4 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	2/3	1		ENSP00000223122	P1	Q9NS00-1
C1GALT1	ENST00000402468.3 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	2/2	1		ENSP00000384550		Q9NS00-2

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

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:

0.000661

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000482

AC:

121

AN:

251048

Hom.:

AF XY:

0.000494

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000679

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000587

AC:

858

AN:

1461470

Hom.:

Cov.:

AF XY:

0.000561

AC XY:

408

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000699

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152306

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000970

Hom.:

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.5

DANN

Benign

0.60

DEOGEN2

Benign

0.060

T;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.65

T;.;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.090

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.63

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.52

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.10

MVP

0.068

MPC

0.12

ClinPred

0.0020

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.23

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