Variant chr20-44504805-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006811.4(SERINC3):c.870A>C(p.Glu290Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,938 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SERINC3
NM_006811.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERINC3	NM_006811.4 linkuse as main transcript	c.870A>C	p.Glu290Asp	missense_variant	7/10	ENST00000342374.5
SERINC3	NM_198941.3 linkuse as main transcript	c.870A>C	p.Glu290Asp	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC3	ENST00000342374.5 linkuse as main transcript	c.870A>C	p.Glu290Asp	missense_variant	7/10	1	NM_006811.4	P1	Q13530-1
SERINC3	ENST00000255175.5 linkuse as main transcript	c.870A>C	p.Glu290Asp	missense_variant	7/11	5		P1	Q13530-1
SERINC3	ENST00000411544.5 linkuse as main transcript	c.87A>C	p.Glu29Asp	missense_variant	1/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250518

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453938

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723356

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 12, 2022

The c.870A>C (p.E290D) alteration is located in exon 7 (coding exon 7) of the SERINC3 gene. This alteration results from a A to C substitution at nucleotide position 870, causing the glutamic acid (E) at amino acid position 290 to be replaced by an aspartic acid (D). 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

T;T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.95

D;D;.

M_CAP

Benign

0.0078

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

4.1

.;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

1.0

.;D;D

Vest4

0.67, 0.67

MutPred

0.49

.;Gain of disorder (P = 0.1913);Gain of disorder (P = 0.1913);

MVP

0.31

MPC

0.40

ClinPred

0.97

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.79

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