Variant 8-2942574-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_033225.6(CSMD1):c.10433G>A(p.Ser3478Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,600,802 control chromosomes in the GnomAD database, including 1,292 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.056 ( 561 hom., cov: 32)

Exomes 𝑓: 0.020 ( 731 hom. )

Consequence

CSMD1
NM_033225.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD1 links:

LOC105377785 (HGNC:):

LOC105377785 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012851655).

BP6

Variant 8-2942574-C-T is Benign according to our data. Variant chr8-2942574-C-T is described in ClinVar as [Benign]. Clinvar id is 3038258.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6 linkuse as main transcript	c.10433G>A	p.Ser3478Asn	missense_variant	69/70	ENST00000635120.2	NP_150094.5	Q96PZ7-1Q59FF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2 linkuse as main transcript	c.10433G>A	p.Ser3478Asn	missense_variant	69/70	5	NM_033225.6	ENSP00000489225.1		Q96PZ7-1

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8523

AN:

152074

Hom.:

556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.0204

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0482

GnomAD3 exomes

AF:

0.0265

AC:

5979

AN:

225504

Hom.:

240

AF XY:

0.0252

AC XY:

3060

AN XY:

121590

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.0210

Gnomad EAS exome

AF:

0.0155

Gnomad SAS exome

AF:

0.0307

Gnomad FIN exome

AF:

0.00324

Gnomad NFE exome

AF:

0.0176

Gnomad OTH exome

AF:

0.0255

GnomAD4 exome

AF:

0.0202

AC:

29248

AN:

1448610

Hom.:

731

Cov.:

AF XY:

0.0202

AC XY:

14520

AN XY:

719072

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.0180

Gnomad4 ASJ exome

AF:

0.0200

Gnomad4 EAS exome

AF:

0.0205

Gnomad4 SAS exome

AF:

0.0306

Gnomad4 FIN exome

AF:

0.00339

Gnomad4 NFE exome

AF:

0.0156

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.0562

AC:

8556

AN:

152192

Hom.:

561

Cov.:

AF XY:

0.0545

AC XY:

4058

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.0205

Gnomad4 SAS

AF:

0.0265

Gnomad4 FIN

AF:

0.00302

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.0477

Alfa

AF:

0.0263

Hom.:

232

Bravo

AF:

0.0621

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.151

AC:

559

ESP6500EA

AF:

0.0179

AC:

146

ExAC

AF:

0.0282

AC:

3396

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CSMD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.39

DANN

Benign

0.16

DEOGEN2

Benign

0.0027

T;.;.;T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.094

T;.;T;T;.;T

MetaRNN

Benign

0.0013

T;T;T;T;T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.33

PROVEAN

Benign

1.6

.;N;.;.;N;.

REVEL

Benign

0.073

Sift

Benign

1.0

.;T;.;.;T;.

Sift4G

Benign

0.98

T;T;T;T;T;T

Polyphen

0.0

.;.;.;.;B;B

Vest4

0.091, 0.10, 0.054, 0.030, 0.048

ClinPred

0.0012

GERP RS

0.56

Varity_R

0.040

gMVP

0.090

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