Variant chr1-31424825-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000373709.8(SERINC2):c.344T>C(p.Met115Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000891 in 1,459,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SERINC2
ENST00000373709.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Variant links:

Genes affected

SERINC2 (HGNC:23231): (serine incorporator 2) Predicted to be involved in several processes, including phosphatidylserine metabolic process; positive regulation of CDP-diacylglycerol-serine O-phosphatidyltransferase activity; and positive regulation of serine C-palmitoyltransferase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SERINC2 links:

SERINC2 (HGNC:):

SERINC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.912

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERINC2	NM_178865.5 linkuse as main transcript	c.344T>C	p.Met115Thr	missense_variant	3/10	ENST00000373709.8	NP_849196.2	Q96SA4-1Q96IM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERINC2	ENST00000373709.8 linkuse as main transcript	c.344T>C	p.Met115Thr	missense_variant	3/10	1	NM_178865.5	ENSP00000362813.3		Q96SA4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000417

AC:

AN:

239748

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000934

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459478

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725988

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:

0.00000990

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

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

Jun 10, 2021

The c.371T>C (p.M124T) alteration is located in exon 4 (coding exon 4) of the SERINC2 gene. This alteration results from a T to C substitution at nucleotide position 371, causing the methionine (M) at amino acid position 124 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

0.24

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

.;.;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.91

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;.;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.9

D;D;D;D

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.038

D;D;D;D

Polyphen

0.14

.;.;B;.

Vest4

0.58

MutPred

0.80

.;.;Gain of helix (P = 0.0696);.;

MVP

0.26

MPC

0.48

ClinPred

0.99

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.89

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