Variant 8-112228859-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198123.2(CSMD3):c.10861A>C(p.Asn3621His) variant causes a missense change. The variant allele was found at a frequency of 0.581 in 1,569,996 control chromosomes in the GnomAD database, including 271,423 homozygotes. In-silico tool predicts 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 0.67 ( 35641 hom., cov: 33)

Exomes 𝑓: 0.57 ( 235782 hom. )

Consequence

CSMD3
NM_198123.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.26

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.572054E-7).

BP6

Variant 8-112228859-T-G is Benign according to our data. Variant chr8-112228859-T-G is described in ClinVar as [Benign]. Clinvar id is 3060958.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 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.10861A>C	p.Asn3621His	missense_variant	70/71	ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10 linkuse as main transcript	c.10861A>C	p.Asn3621His	missense_variant	70/71	1	NM_198123.2	P1	Q7Z407-1

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101397

AN:

151982

Hom.:

35601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.755

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.561

Gnomad OTH

AF:

0.696

GnomAD3 exomes

AF:

0.612

AC:

153171

AN:

250448

Hom.:

48214

AF XY:

0.604

AC XY:

81754

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.900

Gnomad AMR exome

AF:

0.609

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.753

Gnomad SAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.612

GnomAD4 exome

AF:

0.571

AC:

809922

AN:

1417896

Hom.:

235782

Cov.:

AF XY:

0.571

AC XY:

404546

AN XY:

708038

show subpopulations

Gnomad4 AFR exome

AF:

0.902

Gnomad4 AMR exome

AF:

0.607

Gnomad4 ASJ exome

AF:

0.676

Gnomad4 EAS exome

AF:

0.736

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.538

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.610

GnomAD4 genome

AF:

0.667

AC:

101487

AN:

152100

Hom.:

35641

Cov.:

AF XY:

0.661

AC XY:

49126

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.890

Gnomad4 AMR

AF:

0.611

Gnomad4 ASJ

AF:

0.687

Gnomad4 EAS

AF:

0.755

Gnomad4 SAS

AF:

0.586

Gnomad4 FIN

AF:

0.536

Gnomad4 NFE

AF:

0.561

Gnomad4 OTH

AF:

0.692

Alfa

AF:

0.586

Hom.:

63347

Bravo

AF:

0.685

TwinsUK

AF:

0.539

AC:

2000

ALSPAC

AF:

0.558

AC:

2152

ESP6500AA

AF:

0.881

AC:

3881

ESP6500EA

AF:

0.559

AC:

4800

ExAC

AF:

0.614

AC:

74530

Asia WGS

AF:

0.703

AC:

2444

AN:

3472

EpiCase

AF:

0.572

EpiControl

AF:

0.577

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CSMD3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

0.085

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;T;T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.69

T;T;T;T

MetaRNN

Benign

8.6e-7

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;.;.

MutationTaster

Benign

0.0070

P;P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.092

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.58

T;T;T;T

Polyphen

0.99

D;P;.;P

Vest4

0.23

MPC

0.49

ClinPred

0.045

GERP RS

5.6

Varity_R

0.17

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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