chr1-76313936-C-A

Position:

• chr1-76313936-C-A

Variant summary

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

The NM_152996.4(ST6GALNAC3):​c.150C>A​(p.Phe50Leu) 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. 13/21 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: ST6GALNAC3 NM_152996.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

Genes affected

ST6GALNAC3 (HGNC:19343): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 3) ST6GALNAC3 belongs to a family of sialyltransferases that transfer sialic acids from CMP-sialic acid to terminal positions of carbohydrate groups in glycoproteins and glycolipids (Lee et al., 1999 [PubMed 10207017]).[supplied by OMIM, Mar 2008]

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=0.14897242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST6GALNAC3	NM_152996.4	c.150C>A	p.Phe50Leu	missense_variant	2/5	ENST00000328299.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST6GALNAC3	ENST00000328299.4	c.150C>A	p.Phe50Leu	missense_variant	2/5	1	NM_152996.4	P1
ST6GALNAC3	ENST00000464140.1	n.24C>A		non_coding_transcript_exon_variant	1/3	1

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

Oct 25, 2023

The c.150C>A (p.F50L) alteration is located in exon 2 (coding exon 2) of the ST6GALNAC3 gene. This alteration results from a C to A substitution at nucleotide position 150, causing the phenylalanine (F) at amino acid position 50 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	0.32
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	0.94	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.060
Sift	Benign	0.24	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.38
MutPred		0.58		Gain of sheet (P = 0.0344);
MVP		0.030
MPC		0.075
ClinPred		0.42	T
GERP RS		4.2
Varity_R		0.056
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-76779621; COSMIC: COSV100081438;