chr8-113227258-T-C

Variant names:

• chr8-113227258-T-C
• rs2356203
• NM_198123.2:c.514+51334A>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.514+51334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,426 control chromosomes in the GnomAD database, including 36,449 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 0.68 (36449 hom., cov: 31)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD3	NM_198123.2	MANE Select	c.514+51334A>G		intron	N/A	NP_937756.1
	CSMD3	NM_198124.2		c.394+51334A>G		intron	N/A	NP_937757.1
	CSMD3	NM_052900.3		c.514+51334A>G		intron	N/A	NP_443132.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD3	ENST00000297405.10	TSL:1 MANE Select	c.514+51334A>G		intron	N/A	ENSP00000297405.5
	CSMD3	ENST00000343508.7	TSL:1	c.394+51334A>G		intron	N/A	ENSP00000345799.3
	CSMD3	ENST00000455883.2	TSL:1	c.514+51334A>G		intron	N/A	ENSP00000412263.2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102107 AN: 151308 Hom.: 36388 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.675 AC: 102235 AN: 151426 Hom.: 36449 Cov.: 31 AF XY: 0.682 AC XY: 50458 AN XY: 73960

African (AFR) AF: 0.878 AC: 36337 AN: 41408

American (AMR) AF: 0.758 AC: 11474 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1985 AN: 3454

East Asian (EAS) AF: 0.955 AC: 4878 AN: 5110

South Asian (SAS) AF: 0.710 AC: 3423 AN: 4822

European-Finnish (FIN) AF: 0.576 AC: 6081 AN: 10560

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35855 AN: 67630

Other (OTH) AF: 0.688 AC: 1440 AN: 2094

Alfa AF: 0.643 Hom.: 5610

Bravo AF: 0.700

Asia WGS AF: 0.814 AC: 2829 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.052
DANN	Benign	0.42
PhyloP100		-2.5
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: rs2356203; hg19: chr8-114239487;