Variant chr1-31424740-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_178865.5(SERINC2):c.259G>A(p.Asp87Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00507 in 1,610,488 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 28 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 44 hom. )

Consequence

SERINC2
NM_178865.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.55

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010059774).

BP6

Variant 1-31424740-G-A is Benign according to our data. Variant chr1-31424740-G-A is described in ClinVar as [Benign]. Clinvar id is 785935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1824/152312) while in subpopulation AFR AF= 0.0327 (1361/41574). AF 95% confidence interval is 0.0313. There are 28 homozygotes in gnomad4. There are 906 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERINC2	NM_178865.5 linkuse as main transcript	c.259G>A	p.Asp87Asn	missense_variant	3/10	ENST00000373709.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC2	ENST00000373709.8 linkuse as main transcript	c.259G>A	p.Asp87Asn	missense_variant	3/10	1	NM_178865.5	P1	Q96SA4-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1822

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00548

AC:

1320

AN:

240750

Hom.:

AF XY:

0.00484

AC XY:

633

AN XY:

130712

show subpopulations

Gnomad AFR exome

AF:

0.0314

Gnomad AMR exome

AF:

0.00774

Gnomad ASJ exome

AF:

0.00224

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.000371

Gnomad FIN exome

AF:

0.000599

Gnomad NFE exome

AF:

0.00449

Gnomad OTH exome

AF:

0.00696

GnomAD4 exome

AF:

0.00435

AC:

6343

AN:

1458176

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

2964

AN XY:

725118

show subpopulations

Gnomad4 AFR exome

AF:

0.0319

Gnomad4 AMR exome

AF:

0.00851

Gnomad4 ASJ exome

AF:

0.00273

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000304

Gnomad4 FIN exome

AF:

0.000737

Gnomad4 NFE exome

AF:

0.00385

Gnomad4 OTH exome

AF:

0.00669

GnomAD4 genome

AF:

0.0120

AC:

1824

AN:

152312

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

906

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0327

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00378

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.00503

Hom.:

Bravo

AF:

0.0136

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.0297

AC:

131

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00566

AC:

686

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0066

.;.;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

.;.;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.078

Sift

Benign

0.26

T;T;T;T

Sift4G

Benign

0.92

T;T;T;T

Polyphen

0.0040

.;.;B;.

Vest4

0.24

MVP

0.17

MPC

0.10

ClinPred

0.014

GERP RS

4.3

Varity_R

0.23

gMVP

0.46

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