Genetic Variant SNED1:p.Val192Val (chr2-241033809-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001080437.3(SNED1):c.576G>A(p.Val192Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,610,930 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

SNED1
NM_001080437.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.37

Variant links:

Genes affected

SNED1 (HGNC:24696): (sushi, nidogen and EGF like domains 1) Predicted to enable Notch binding activity. Predicted to be involved in cell-matrix adhesion. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SNED1 links:

SNED1-AS1 (HGNC:41060): (SNED1 antisense RNA 1)

SNED1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-241033809-G-A is Benign according to our data. Variant chr2-241033809-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652103.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNED1	NM_001080437.3 link	c.576G>A	p.Val192Val	synonymous_variant	Exon 3 of 32	ENST00000310397.13	NP_001073906.1	Q8TER0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SNED1	ENST00000310397.13 link	c.576G>A	p.Val192Val	synonymous_variant	Exon 3 of 32	5	NM_001080437.3	ENSP00000308893.8	Q8TER0-1
SNED1	ENST00000405547.7 link	c.576G>A	p.Val192Val	synonymous_variant	Exon 3 of 30	5		ENSP00000386007.3	Q8TER0-3
SNED1	ENST00000401884.5 link	c.576G>A	p.Val192Val	synonymous_variant	Exon 3 of 27	5		ENSP00000384871.1	Q8TER0-5
SNED1-AS1	ENST00000458377.1 link	n.38-206C>T		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.000788

AC:

120

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000595

AC:

145

AN:

243540

Hom.:

AF XY:

0.000633

AC XY:

AN XY:

132646

show subpopulations

Gnomad AFR exome

AF:

0.0000681

Gnomad AMR exome

AF:

0.000353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000234

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.00127

AC:

1853

AN:

1458596

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

914

AN XY:

725314

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000315

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000326

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152334

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000895

Hom.:

Bravo

AF:

0.000858

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SNED1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

DANN

Benign

0.77

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