Variant chr1-77044288-C-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.346C>A(p.Gln116Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ST6GALNAC5
NM_030965.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

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=0.15089789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ST6GALNAC5	NM_030965.3 linkuse as main transcript	c.346C>A	p.Gln116Lys	missense_variant	3/5	ENST00000477717.6	NP_112227.1
ST6GALNAC5	NM_001320273.2 linkuse as main transcript	c.262-5970C>A		intron_variant			NP_001307202.1
ST6GALNAC5	NM_001320274.2 linkuse as main transcript	c.262-18687C>A		intron_variant			NP_001307203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ST6GALNAC5	ENST00000477717.6 linkuse as main transcript	c.346C>A	p.Gln116Lys	missense_variant	3/5	1	NM_030965.3	ENSP00000417583	P1
ST6GALNAC5	ENST00000488940.1 linkuse as main transcript	n.149C>A		non_coding_transcript_exon_variant	2/3	5
ST6GALNAC5	ENST00000318803.6 linkuse as main transcript	c.346C>A	p.Gln116Lys	missense_variant, NMD_transcript_variant	3/5	5		ENSP00000436263

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251182

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

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

Nov 08, 2022

The c.346C>A (p.Q116K) alteration is located in exon 3 (coding exon 3) of the ST6GALNAC5 gene. This alteration results from a C to A substitution at nucleotide position 346, causing the glutamine (Q) at amino acid position 116 to be replaced by a lysine (K). 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

0.085

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.014

Eigen

Benign

-0.060

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.70

M_CAP

Benign

0.011

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.88

REVEL

Benign

0.037

Sift

Benign

0.31

Sift4G

Benign

0.53

Polyphen

0.036

Vest4

0.44

MutPred

0.49

Gain of methylation at Q116 (P = 0.0244);

MVP

0.082

MPC

0.50

ClinPred

0.092

GERP RS

4.7

Varity_R

0.32

gMVP

0.44

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