1-76868635-G-A

Position:

• chr1-76868635-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030965.3(ST6GALNAC5):​c.154G>A​(p.Ala52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ST6GALNAC5 NM_030965.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30

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]

ACMG classification

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=0.117168546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST6GALNAC5	NM_030965.3	c.154G>A	p.Ala52Thr	missense_variant	2/5	ENST00000477717.6	NP_112227.1
ST6GALNAC5	NM_001320273.2	c.154G>A	p.Ala52Thr	missense_variant	2/4		NP_001307202.1
ST6GALNAC5	NM_001320274.2	c.154G>A	p.Ala52Thr	missense_variant	2/3		NP_001307203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST6GALNAC5	ENST00000477717.6	c.154G>A	p.Ala52Thr	missense_variant	2/5	1	NM_030965.3	ENSP00000417583	P1
ST6GALNAC5	ENST00000480428.1	n.350G>A		non_coding_transcript_exon_variant	2/3	4
ST6GALNAC5	ENST00000496845.1	n.348G>A		non_coding_transcript_exon_variant	2/2	2
ST6GALNAC5	ENST00000318803.6	c.154G>A	p.Ala52Thr	missense_variant, NMD_transcript_variant	2/5	5		ENSP00000436263

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.154G>A (p.A52T) 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 154, causing the alanine (A) at amino acid position 52 to be replaced by a threonine (T). 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	0.068
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.067
Sift	Benign	0.14	T
Sift4G	Benign	0.74	T
Polyphen		0.049	B
Vest4		0.30
MutPred		0.30		Gain of relative solvent accessibility (P = 0.005);
MVP		0.068
MPC		0.33
ClinPred		0.15	T
GERP RS		4.0
Varity_R		0.066
gMVP		0.28

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

Other links and lift over

dbSNP: rs1225692560; hg19: chr1-77334320;