Variant 6-122453767-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_020755.4(SERINC1):c.589+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00738 in 1,595,748 control chromosomes in the GnomAD database, including 51 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 0.0049 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 44 hom. )

Consequence

SERINC1
NM_020755.4 splice_region, intron

Scores

Splicing: ADA: 0.06135

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.50

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 6-122453767-T-C is Benign according to our data. Variant chr6-122453767-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656895.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERINC1	NM_020755.4 linkuse as main transcript	c.589+3A>G		splice_region_variant, intron_variant		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.589+3A>G		splice_region_variant, intron_variant		1	NM_020755.4	ENSP00000342962.3		Q9NRX5

Frequencies

GnomAD3 genomes

AF:

0.00491

AC:

748

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00801

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00462

AC:

1143

AN:

247524

Hom.:

AF XY:

0.00474

AC XY:

635

AN XY:

133926

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.000906

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.00854

Gnomad NFE exome

AF:

0.00712

Gnomad OTH exome

AF:

0.00535

GnomAD4 exome

AF:

0.00764

AC:

11032

AN:

1443438

Hom.:

Cov.:

AF XY:

0.00751

AC XY:

5385

AN XY:

716668

show subpopulations

Gnomad4 AFR exome

AF:

0.000847

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.00105

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.00734

Gnomad4 NFE exome

AF:

0.00910

Gnomad4 OTH exome

AF:

0.00578

GnomAD4 genome

AF:

0.00490

AC:

747

AN:

152310

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

357

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.00800

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00603

Hom.:

Bravo

AF:

0.00408

Asia WGS

AF:

0.000577

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

May 01, 2023

SERINC1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.061

dbscSNV1_RF

Benign

0.23

SpliceAI score (max)

0.030

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