Variant chr1-77044403-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.461G>A(p.Arg154His) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,612,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R154C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ST6GALNAC5
NM_030965.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63

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:

ST6GALNAC5 (HGNC:):

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=0.25535002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST6GALNAC5	NM_030965.3 linkuse as main transcript	c.461G>A	p.Arg154His	missense_variant	3/5	ENST00000477717.6	NP_112227.1	Q9BVH7
ST6GALNAC5	NM_001320273.2 linkuse as main transcript	c.262-5855G>A		intron_variant			NP_001307202.1	B4DV27
ST6GALNAC5	NM_001320274.2 linkuse as main transcript	c.262-18572G>A		intron_variant			NP_001307203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ST6GALNAC5	ENST00000477717.6 linkuse as main transcript	c.461G>A	p.Arg154His	missense_variant	3/5	1	NM_030965.3	ENSP00000417583.1	Q9BVH7
ST6GALNAC5	ENST00000318803.6 linkuse as main transcript	n.461G>A		non_coding_transcript_exon_variant	3/5	5		ENSP00000436263.1	F2Z2C8
ST6GALNAC5	ENST00000488940.1 linkuse as main transcript	n.264G>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250054

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

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:

0.00000548

AC:

AN:

1460756

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726660

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

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

Feb 27, 2023

The c.461G>A (p.R154H) alteration is located in exon 3 (coding exon 3) of the ST6GALNAC5 gene. This alteration results from a G to A substitution at nucleotide position 461, causing the arginine (R) at amino acid position 154 to be replaced by a histidine (H). 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

-0.33

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0096

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.12

Sift

Uncertain

0.018

Sift4G

Uncertain

0.058

Polyphen

0.27

Vest4

0.43

MutPred

0.49

Loss of MoRF binding (P = 0.0056);

MVP

0.21

MPC

0.52

ClinPred

0.95

GERP RS

4.6

Varity_R

0.37

gMVP

0.64

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