16-70395071-C-G

Variant names:

• chr16-70395071-C-G
• NM_006927.4:c.444G>C

Variant summary

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

The NM_006927.4(ST3GAL2):​c.444G>C​(p.Gln148His) 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: ST3GAL2 NM_006927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59

Genes affected

ST3GAL2 (HGNC:10863): (ST3 beta-galactoside alpha-2,3-sialyltransferase 2) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi but can be proteolytically processed to a soluble form. This protein, which is a member of glycosyltransferase family 29, can use the same acceptor substrates as does sialyltransferase 4A. [provided by RefSeq, Jul 2008]

ENSG00000260111 (HGNC:):

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=0.13808453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL2	NM_006927.4	c.444G>C	p.Gln148His	missense_variant	Exon 3 of 7	ENST00000342907.3	NP_008858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL2	ENST00000342907.3	c.444G>C	p.Gln148His	missense_variant	Exon 3 of 7	5	NM_006927.4	ENSP00000345477.2
ST3GAL2	ENST00000393640.8	c.444G>C	p.Gln148His	missense_variant	Exon 2 of 6	1		ENSP00000377257.4
ENSG00000260111	ENST00000566960.1	n.211-4052C>G		intron_variant	Intron 1 of 1	3

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

Oct 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.444G>C (p.Q148H) alteration is located in exon 3 (coding exon 2) of the ST3GAL2 gene. This alteration results from a G to C substitution at nucleotide position 444, causing the glutamine (Q) at amino acid position 148 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	0.093
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.18	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.99	N;N
REVEL	Benign	0.096
Sift	Benign	0.18	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.0	B;B
Vest4		0.23
MutPred		0.57		Gain of methylation at R151 (P = 0.0745);Gain of methylation at R151 (P = 0.0745);
MVP		0.043
MPC		0.84
ClinPred		0.78	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.089
gMVP		0.58

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: chr16-70428974;