Variant 1-76868705-G-T 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.224G>T(p.Arg75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,380,760 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: 0.0000014 ( 0 hom. )

Consequence

ST6GALNAC5
NM_030965.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.372

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=0.109137714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST6GALNAC5	NM_030965.3 linkuse as main transcript	c.224G>T	p.Arg75Leu	missense_variant	2/5	ENST00000477717.6	NP_112227.1	Q9BVH7
ST6GALNAC5	NM_001320273.2 linkuse as main transcript	c.224G>T	p.Arg75Leu	missense_variant	2/4		NP_001307202.1	B4DV27
ST6GALNAC5	NM_001320274.2 linkuse as main transcript	c.224G>T	p.Arg75Leu	missense_variant	2/3		NP_001307203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ST6GALNAC5	ENST00000477717.6 linkuse as main transcript	c.224G>T	p.Arg75Leu	missense_variant	2/5	1	NM_030965.3	ENSP00000417583.1	Q9BVH7
ST6GALNAC5	ENST00000318803.6 linkuse as main transcript	n.224G>T		non_coding_transcript_exon_variant	2/5	5		ENSP00000436263.1	F2Z2C8
ST6GALNAC5	ENST00000480428.1 linkuse as main transcript	n.420G>T		non_coding_transcript_exon_variant	2/3	4
ST6GALNAC5	ENST00000496845.1 linkuse as main transcript	n.418G>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1380760

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680884

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:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 28, 2023

The c.224G>T (p.R75L) alteration is located in exon 2 (coding exon 2) of the ST6GALNAC5 gene. This alteration results from a G to T substitution at nucleotide position 224, causing the arginine (R) at amino acid position 75 to be replaced by a leucine (L). 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

0.097

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0041

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.65

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.79

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.67

REVEL

Benign

0.20

Sift

Benign

0.45

Sift4G

Benign

0.38

Polyphen

0.19

Vest4

0.29

MutPred

0.62

Loss of methylation at R75 (P = 0.0528);

MVP

0.15

MPC

0.48

ClinPred

0.35

GERP RS

4.2

Varity_R

0.18

gMVP

0.31

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