chr1-43736265-G-A

Position:

• chr1-43736265-G-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_006279.5(ST3GAL3):​c.3G>A​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST3GAL3 NM_006279.5 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.71

Genes affected

ST3GAL3 (HGNC:10866): (ST3 beta-galactoside alpha-2,3-sialyltransferase 3) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ENSG00000284989 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.3G>A	p.Met1?	start_lost	2/12	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.3G>A	p.Met1?	start_lost	2/12	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*1325G>A		non_coding_transcript_exon_variant	16/26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*1325G>A		3_prime_UTR_variant	16/26			ENSP00000494063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 03, 2022

This variant has not been reported in the literature in individuals affected with ST3GAL3-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1402972). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the ST3GAL3 mRNA. The next in-frame methionine is located at codon 95. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;.;.
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.36	D
PROVEAN	Benign	-1.2	N;N;N;D;N;N;N;.;.;.;N;.;N;.;N;.;.;N;.;N;.;.;N;.;N;D;N;N;N;N;D;N;D;N
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;.;.;.;D;.;D;.;D;.;.;D;.;D;.;.;D;.;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;.;.;.;D;.;D;.;D;.;.;D;.;D;.;.;D;.;D;D;D;D;D;D;D;D;D;D
Polyphen		0.53	P;P;P;.;P;P;P;.;.;.;.;.;P;P;P;P;.;D;.;.;.;P;.;.;P;P;P;P;.;P;P;P;.;P
Vest4		0.81
MutPred		0.94		Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);Gain of catalytic residue at M1 (P = 0.0062);
MVP		0.96
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.74
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-44201936;