7-7238816-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0250

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]

ACMG classification

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	UniProt
C1GALT1	NM_020156.5	c.782T>C	p.Ile261Thr	missense_variant	3/4	ENST00000436587.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1GALT1	ENST00000436587.7	c.782T>C	p.Ile261Thr	missense_variant	3/4	5	NM_020156.5	P1
C1GALT1	ENST00000223122.4	c.782T>C	p.Ile261Thr	missense_variant	2/3	1		P1
C1GALT1	ENST00000402468.3	c.782T>C	p.Ile261Thr	missense_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.000828 AC: 126 AN: 152188 Hom.: 0 Cov.: 33

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.: 0 AF XY: 0.000494 AC XY: 67 AN XY: 135690

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.: 0 Cov.: 32 AF XY: 0.000561 AC XY: 408 AN XY: 727042

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.: 0 Cov.: 33 AF XY: 0.00101 AC XY: 75 AN XY: 74480

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.: 87

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000420 AC: 51

EpiCase AF: 0.000436

EpiControl AF: 0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
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	N
LIST_S2	Benign	0.65	T;.;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.0061	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.090	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
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	T
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

Other links and lift over

dbSNP: rs61744815; hg19: chr7-7278447;