Variant 8-112241725-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_198123.2(CSMD3):c.10463T>C(p.Leu3488Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,609,456 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 19 hom., cov: 32)

Exomes 𝑓: 0.022 ( 412 hom. )

Consequence

CSMD3
NM_198123.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.25

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005859643).

BP6

Variant 8-112241725-A-G is Benign according to our data. Variant chr8-112241725-A-G is described in ClinVar as [Benign]. Clinvar id is 3038391.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0153 (2331/152220) while in subpopulation NFE AF= 0.022 (1497/67992). AF 95% confidence interval is 0.0211. There are 19 homozygotes in gnomad4. There are 1159 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 2336 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD3	NM_198123.2 linkuse as main transcript	c.10463T>C	p.Leu3488Pro	missense_variant	66/71	ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10 linkuse as main transcript	c.10463T>C	p.Leu3488Pro	missense_variant	66/71	1	NM_198123.2	P1	Q7Z407-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2336

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00401

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.0226

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0178

AC:

4479

AN:

251366

Hom.:

AF XY:

0.0187

AC XY:

2545

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0180

Gnomad FIN exome

AF:

0.0229

Gnomad NFE exome

AF:

0.0237

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0219

AC:

31896

AN:

1457236

Hom.:

412

Cov.:

AF XY:

0.0222

AC XY:

16068

AN XY:

725238

show subpopulations

Gnomad4 AFR exome

AF:

0.00264

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0175

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.0216

Gnomad4 NFE exome

AF:

0.0240

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0153

AC:

2331

AN:

152220

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1159

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00399

Gnomad4 AMR

AF:

0.0161

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0162

Gnomad4 FIN

AF:

0.0226

Gnomad4 NFE

AF:

0.0220

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0217

Hom.:

Bravo

AF:

0.0150

TwinsUK

AF:

0.0210

AC:

ALSPAC

AF:

0.0218

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0252

AC:

217

ExAC

AF:

0.0172

AC:

2093

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0293

EpiControl

AF:

0.0282

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

Apr 16, 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

0.32

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.074

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.82

T;T;T;T

MetaRNN

Benign

0.0059

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Benign

0.18

Sift

Benign

0.16

T;T;D;T

Sift4G

Uncertain

0.030

D;D;D;D

Polyphen

0.0010

B;B;.;P

Vest4

0.90

MPC

0.42

ClinPred

0.045

GERP RS

5.2

Varity_R

0.53

gMVP

0.72

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