Variant 8-112234358-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198123.2(CSMD3):c.10740+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,547,270 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 4 hom. )

Consequence

CSMD3
NM_198123.2 splice_region, intron

Scores

Splicing: ADA: 0.00007022

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.199

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-112234358-T-C is Benign according to our data. Variant chr8-112234358-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658756.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 66 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD3	NM_198123.2 linkuse as main transcript	c.10740+7A>G		splice_region_variant, intron_variant		ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10 linkuse as main transcript	c.10740+7A>G		splice_region_variant, intron_variant		1	NM_198123.2	P1	Q7Z407-1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000794

AC:

199

AN:

250628

Hom.:

AF XY:

0.000708

AC XY:

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000946

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000451

AC:

629

AN:

1395096

Hom.:

Cov.:

AF XY:

0.000464

AC XY:

324

AN XY:

698316

show subpopulations

Gnomad4 AFR exome

AF:

0.0000621

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000950

Gnomad4 NFE exome

AF:

0.000188

Gnomad4 OTH exome

AF:

0.000980

GnomAD4 genome

AF:

0.000434

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.000495

EpiCase

AF:

0.000274

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

CSMD3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.2

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000070

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.080

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