Variant chr20-44506853-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006811.4(SERINC3):c.757A>G(p.Ile253Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,592,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

SERINC3
NM_006811.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.871

Variant links:

Genes affected

SERINC3 (HGNC:11699): (serine incorporator 3) Predicted to enable L-serine transmembrane transporter activity. Involved in defense response to virus; detection of virus; and innate immune response. Predicted to be located in Golgi apparatus. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SERINC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040558428).

BP6

Variant 20-44506853-T-C is Benign according to our data. Variant chr20-44506853-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2554855.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERINC3	NM_006811.4 linkuse as main transcript	c.757A>G	p.Ile253Val	missense_variant	6/10	ENST00000342374.5
SERINC3	NM_198941.3 linkuse as main transcript	c.757A>G	p.Ile253Val	missense_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC3	ENST00000342374.5 linkuse as main transcript	c.757A>G	p.Ile253Val	missense_variant	6/10	1	NM_006811.4	P1	Q13530-1
SERINC3	ENST00000255175.5 linkuse as main transcript	c.757A>G	p.Ile253Val	missense_variant	6/11	5		P1	Q13530-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

236256

Hom.:

AF XY:

0.0000235

AC XY:

AN XY:

127904

show subpopulations

Gnomad AFR exome

AF:

0.0000637

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:

0.0000273

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000507

AC:

AN:

1440128

Hom.:

Cov.:

AF XY:

0.0000531

AC XY:

AN XY:

715800

show subpopulations

Gnomad4 AFR exome

AF:

0.000245

Gnomad4 AMR exome

AF:

0.0000247

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000453

Gnomad4 OTH exome

AF:

0.000219

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0020

DANN

Benign

0.30

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.57

T;.

M_CAP

Benign

0.0019

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.15

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.27

N;N

REVEL

Benign

0.075

Sift

Benign

0.91

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.13

MVP

0.23

MPC

0.067

ClinPred

0.014

GERP RS

-7.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.38

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