Variant chr1-31424845-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_178865.5(SERINC2):c.364C>T(p.Arg122Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,611,598 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R122G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0043 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 34 hom. )

Consequence

SERINC2
NM_178865.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019129515).

BP6

Variant 1-31424845-C-T is Benign according to our data. Variant chr1-31424845-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638601.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERINC2	NM_178865.5 linkuse as main transcript	c.364C>T	p.Arg122Trp	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.364C>T	p.Arg122Trp	missense_variant	3/10	1	NM_178865.5	P1	Q96SA4-1

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

653

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00800

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00402

AC:

959

AN:

238622

Hom.:

AF XY:

0.00408

AC XY:

535

AN XY:

131058

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.000646

Gnomad ASJ exome

AF:

0.00401

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00265

Gnomad NFE exome

AF:

0.00746

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00610

AC:

8898

AN:

1459374

Hom.:

Cov.:

AF XY:

0.00609

AC XY:

4422

AN XY:

725892

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.000606

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00330

Gnomad4 NFE exome

AF:

0.00750

Gnomad4 OTH exome

AF:

0.00367

GnomAD4 genome

AF:

0.00429

AC:

653

AN:

152224

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

284

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00800

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00657

Hom.:

Bravo

AF:

0.00374

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00208

AC:

ESP6500EA

AF:

0.00790

AC:

ExAC

AF:

0.00392

AC:

473

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

SERINC2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.0090

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-5.4

D;D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.29

MVP

0.41

MPC

0.098

ClinPred

0.047

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.46

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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