Genetic Variant CSMD1:p.Asn1497Ser (chr8-3219437-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033225.6(CSMD1):c.4490A>G(p.Asn1497Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,480,760 control chromosomes in the GnomAD database, including 13,111 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1172 hom., cov: 32)

Exomes 𝑓: 0.13 ( 11939 hom. )

Consequence

CSMD1
NM_033225.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001791805).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6 link	c.4490A>G	p.Asn1497Ser	missense_variant	Exon 29 of 70	ENST00000635120.2	NP_150094.5	Q96PZ7-1Q59FF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2 link	c.4490A>G	p.Asn1497Ser	missense_variant	Exon 29 of 70	5	NM_033225.6	ENSP00000489225.1		Q96PZ7-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16340

AN:

152086

Hom.:

1169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0271

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.0818

Gnomad EAS

AF:

0.0518

Gnomad SAS

AF:

0.0803

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.0944

GnomAD3 exomes

AF:

0.127

AC:

14070

AN:

110382

Hom.:

1023

AF XY:

0.127

AC XY:

7410

AN XY:

58156

show subpopulations

Gnomad AFR exome

AF:

0.0272

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.0820

Gnomad EAS exome

AF:

0.0528

Gnomad SAS exome

AF:

0.0927

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.131

AC:

173863

AN:

1328556

Hom.:

11939

Cov.:

AF XY:

0.130

AC XY:

84264

AN XY:

650596

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.0805

Gnomad4 EAS exome

AF:

0.0561

Gnomad4 SAS exome

AF:

0.0893

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.107

AC:

16352

AN:

152204

Hom.:

1172

Cov.:

AF XY:

0.109

AC XY:

8102

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0270

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.0818

Gnomad4 EAS

AF:

0.0521

Gnomad4 SAS

AF:

0.0807

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.0963

Alfa

AF:

0.120

Hom.:

1586

Bravo

AF:

0.102

TwinsUK

AF:

0.133

AC:

495

ALSPAC

AF:

0.138

AC:

530

ESP6500AA

AF:

0.0263

AC:

ESP6500EA

AF:

0.129

AC:

1058

ExAC

AF:

0.0903

AC:

10420

Asia WGS

AF:

0.0790

AC:

276

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0090

T;.;.;.;T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

D;.;D;D;.;D

MetaRNN

Benign

0.0018

T;T;T;T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.84

.;N;.;.;N;.

REVEL

Benign

0.13

Sift

Benign

0.76

.;T;.;.;T;.

Sift4G

Benign

0.73

T;T;T;T;T;T

Polyphen

0.0

.;.;.;.;B;B

Vest4

0.27, 0.27, 0.26, 0.14, 0.25

ClinPred

0.0012

GERP RS

3.0

Varity_R

0.049

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over