rs2052339

Variant names:

• chr8-112285664-T-C
• rs2052339
• NM_198123.2:c.9331+1400A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198123.2(CSMD3):​c.9331+1400A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,088 control chromosomes in the GnomAD database, including 3,654 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 0.20 (3654 hom., cov: 32)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 1 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.9331+1400A>G		intron_variant	Intron 58 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.9331+1400A>G		intron_variant	Intron 58 of 70	1	NM_198123.2	ENSP00000297405.5
CSMD3	ENST00000343508.7	c.9211+1400A>G		intron_variant	Intron 59 of 71	1		ENSP00000345799.3
CSMD3	ENST00000455883.2	c.8824+1400A>G		intron_variant	Intron 56 of 68	1		ENSP00000412263.2
CSMD3	ENST00000339701.7	c.7141+1400A>G		intron_variant	Intron 43 of 55	1		ENSP00000341558.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30522 AN: 151970 Hom.: 3652 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.236

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.201 AC: 30523 AN: 152088 Hom.: 3654 Cov.: 32 AF XY: 0.203 AC XY: 15053 AN XY: 74330

African (AFR) AF: 0.0742 AC: 3081 AN: 41534

American (AMR) AF: 0.290 AC: 4427 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3472

East Asian (EAS) AF: 0.361 AC: 1864 AN: 5166

South Asian (SAS) AF: 0.289 AC: 1393 AN: 4820

European-Finnish (FIN) AF: 0.214 AC: 2265 AN: 10578

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15613 AN: 67954

Other (OTH) AF: 0.235 AC: 495 AN: 2104

Alfa AF: 0.203 Hom.: 456

Bravo AF: 0.201

Asia WGS AF: 0.314 AC: 1092 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.8
DANN	Benign	0.69
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2052339; hg19: chr8-113297893;