Variant chr6-122447004-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_020755.4(SERINC1):c.996C>T(p.Ser332Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00917 in 1,602,040 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 81 hom. )

Consequence

SERINC1
NM_020755.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0006381

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.57

Variant links:

Genes affected

SERINC1 (HGNC:13464): (serine incorporator 1) Predicted to enable protein-macromolecule adaptor activity. 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. Predicted to be located in endoplasmic reticulum membrane and plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SERINC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 6-122447004-G-A is Benign according to our data. Variant chr6-122447004-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656893.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.57 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERINC1	NM_020755.4 linkuse as main transcript	c.996C>T	p.Ser332Ser	splice_region_variant, synonymous_variant	9/10	ENST00000339697.5	NP_065806.1	Q9NRX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERINC1	ENST00000339697.5 linkuse as main transcript	c.996C>T	p.Ser332Ser	splice_region_variant, synonymous_variant	9/10	1	NM_020755.4	ENSP00000342962.3		Q9NRX5

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1047

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00678

AC:

1701

AN:

250762

Hom.:

AF XY:

0.00691

AC XY:

937

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00314

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.00979

Gnomad OTH exome

AF:

0.00851

GnomAD4 exome

AF:

0.00941

AC:

13644

AN:

1449834

Hom.:

Cov.:

AF XY:

0.00932

AC XY:

6733

AN XY:

722134

show subpopulations

Gnomad4 AFR exome

AF:

0.00226

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00344

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00866

GnomAD4 genome

AF:

0.00688

AC:

1047

AN:

152206

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

501

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0147

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00856

Hom.:

Bravo

AF:

0.00579

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00932

EpiControl

AF:

0.00895

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

Mar 01, 2024

SERINC1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00064

dbscSNV1_RF

Benign

0.15

SpliceAI score (max)

0.070

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