Variant chr1-76868554-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030965.3(ST6GALNAC5):c.73G>A(p.Val25Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,106 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: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ST6GALNAC5
NM_030965.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

ST6GALNAC5 (HGNC:19342): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 5) The protein encoded by this gene is a Golgi type II transmembrane glycosyltransferase. The encoded protein catalyzes the transfer of sialic acid to cell surface proteins to modulate cell-cell interactions. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ST6GALNAC5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10865325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ST6GALNAC5	NM_030965.3 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	2/5	ENST00000477717.6	NP_112227.1
ST6GALNAC5	NM_001320273.2 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	2/4		NP_001307202.1
ST6GALNAC5	NM_001320274.2 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	2/3		NP_001307203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ST6GALNAC5	ENST00000477717.6 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	2/5	1	NM_030965.3	ENSP00000417583	P1
ST6GALNAC5	ENST00000480428.1 linkuse as main transcript	n.269G>A		non_coding_transcript_exon_variant	2/3	4
ST6GALNAC5	ENST00000496845.1 linkuse as main transcript	n.267G>A		non_coding_transcript_exon_variant	2/2	2
ST6GALNAC5	ENST00000318803.6 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant, NMD_transcript_variant	2/5	5		ENSP00000436263

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246930

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133996

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000908

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461106

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Sep 26, 2023

The c.73G>A (p.V25M) alteration is located in exon 2 (coding exon 2) of the ST6GALNAC5 gene. This alteration results from a G to A substitution at nucleotide position 73, causing the valine (V) at amino acid position 25 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.014

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.78

M_CAP

Benign

0.025

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.11

MutationTaster

Benign

0.87

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.36

REVEL

Benign

0.075

Sift

Benign

0.38

Sift4G

Benign

0.52

Polyphen

0.015

Vest4

0.27

MutPred

0.41

Gain of disorder (P = 0.034);

MVP

0.068

MPC

0.35

ClinPred

0.21

GERP RS

3.6

Varity_R

0.059

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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