Variant 8-112224816-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_198123.2(CSMD3):c.11079G>A(p.Ala3693=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,613,672 control chromosomes in the GnomAD database, including 10,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.087 ( 762 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9617 hom. )

Consequence

CSMD3
NM_198123.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.67

Variant links:

Genes affected

CSMD3 (HGNC:19291): (CUB and Sushi multiple domains 3) Predicted to be involved in regulation of dendrite development. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 8-112224816-C-T is Benign according to our data. Variant chr8-112224816-C-T is described in ClinVar as [Benign]. Clinvar id is 3056930.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD3	NM_198123.2 linkuse as main transcript	c.11079G>A	p.Ala3693=	synonymous_variant	71/71	ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10 linkuse as main transcript	c.11079G>A	p.Ala3693=	synonymous_variant	71/71	1	NM_198123.2	P1	Q7Z407-1

Frequencies

GnomAD3 genomes

AF:

0.0871

AC:

13248

AN:

152048

Hom.:

761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.0843

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0652

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0971

AC:

24414

AN:

251424

Hom.:

1490

AF XY:

0.0999

AC XY:

13570

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.0663

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.00174

Gnomad SAS exome

AF:

0.0760

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.111

AC:

161762

AN:

1461506

Hom.:

9617

Cov.:

AF XY:

0.110

AC XY:

79873

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0206

Gnomad4 AMR exome

AF:

0.0673

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.00186

Gnomad4 SAS exome

AF:

0.0765

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.0870

AC:

13242

AN:

152166

Hom.:

762

Cov.:

AF XY:

0.0879

AC XY:

6542

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0205

Gnomad4 AMR

AF:

0.0841

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0659

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.117

Hom.:

1894

Bravo

AF:

0.0787

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

EpiCase

AF:

0.130

EpiControl

AF:

0.135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CSMD3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 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

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.3

DANN

Benign

0.67

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