dbSNP rs10505182: CSMD3:c.9863-442C>A (chr8-112255869-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198123.2(CSMD3):c.9863-442C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 169,220 control chromosomes in the GnomAD database, including 3,250 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2907 hom., cov: 32)

Exomes 𝑓: 0.19 ( 343 hom. )

Consequence

CSMD3
NM_198123.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CSMD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198123.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSMD3	NM_198123.2	MANE Select	c.9863-442C>A	intron	N/A	NP_937756.1	Q7Z407-1
CSMD3	NM_198124.2		c.9743-442C>A	intron	N/A	NP_937757.1	Q7Z407-2
CSMD3	NM_052900.3		c.9356-442C>A	intron	N/A	NP_443132.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSMD3	ENST00000297405.10	TSL:1 MANE Select	c.9863-442C>A	intron	N/A	ENSP00000297405.5	Q7Z407-1
CSMD3	ENST00000343508.7	TSL:1	c.9743-442C>A	intron	N/A	ENSP00000345799.3	Q7Z407-2
CSMD3	ENST00000455883.2	TSL:1	c.9356-442C>A	intron	N/A	ENSP00000412263.2	Q7Z407-3

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27046

AN:

151880

Hom.:

2908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0667

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.0839

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.190

AC:

3271

AN:

17220

Hom.:

343

Cov.:

AF XY:

0.185

AC XY:

1735

AN XY:

9388

show subpopulations

African (AFR)

AF:

0.0733

AC:

AN:

150

American (AMR)

AF:

0.175

AC:

339

AN:

1938

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

AN:

220

East Asian (EAS)

AF:

0.0507

AC:

AN:

828

South Asian (SAS)

AF:

0.141

AC:

313

AN:

2222

European-Finnish (FIN)

AF:

0.228

AC:

106

AN:

464

Middle Eastern (MID)

AF:

0.429

AC:

AN:

European-Non Finnish (NFE)

AF:

0.211

AC:

2223

AN:

10560

Other (OTH)

AF:

0.216

AC:

172

AN:

796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

132

265

397

530

662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.178

AC:

27046

AN:

152000

Hom.:

2907

Cov.:

AF XY:

0.176

AC XY:

13078

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0666

AC:

2766

AN:

41508

American (AMR)

AF:

0.159

AC:

2419

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1015

AN:

3468

East Asian (EAS)

AF:

0.0843

AC:

435

AN:

5162

South Asian (SAS)

AF:

0.133

AC:

642

AN:

4822

European-Finnish (FIN)

AF:

0.265

AC:

2793

AN:

10536

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.239

AC:

16218

AN:

67934

Other (OTH)

AF:

0.207

AC:

439

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1095

2189

3284

4378

5473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.211

Hom.:

2256

Bravo

AF:

0.167

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.041

(source)

DANN

Benign

0.46

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over