Variant 8-2938686-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033225.6(CSMD1):c.10594G>A(p.Ala3532Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CSMD1
NM_033225.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3449757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6 linkuse as main transcript	c.10594G>A	p.Ala3532Thr	missense_variant	70/70	ENST00000635120.2
LOC105377785	NR_168443.1 linkuse as main transcript	n.1172-69882C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2 linkuse as main transcript	c.10594G>A	p.Ala3532Thr	missense_variant	70/70	5	NM_033225.6	P4	Q96PZ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242752

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000920

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459560

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.10594G>A (p.A3532T) alteration is located in exon 70 (coding exon 70) of the CSMD1 gene. This alteration results from a G to A substitution at nucleotide position 10594, causing the alanine (A) at amino acid position 3532 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.067

T;.;.;.;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

D;.;D;D;.;D

M_CAP

Benign

0.0084

MetaRNN

Benign

0.34

T;T;T;T;T;T

MetaSVM

Benign

-0.42

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.78

REVEL

Benign

0.24

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Polyphen

0.64

.;.;.;.;P;P

Vest4

0.74, 0.83, 0.77, 0.77, 0.78

MutPred

0.22

.;.;.;.;Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);

MVP

0.55

ClinPred

0.94

GERP RS

5.9

Varity_R

0.59

gMVP

0.55

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