rs10505196

Variant names:

• chr8-112949729-A-C
• rs10505196
• NM_198123.2:c.1421-1852T>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.1421-1852T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,864 control chromosomes in the GnomAD database, including 14,672 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 0.43 (14672 hom., cov: 32)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.863
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD3	NM_198123.2	MANE Select	c.1421-1852T>G		intron	N/A	NP_937756.1	Q7Z407-1
	CSMD3	NM_198124.2		c.1301-1852T>G		intron	N/A	NP_937757.1	Q7Z407-2
	CSMD3	NM_052900.3		c.1109-1852T>G		intron	N/A	NP_443132.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD3	ENST00000297405.10	TSL:1 MANE Select	c.1421-1852T>G		intron	N/A	ENSP00000297405.5	Q7Z407-1
	CSMD3	ENST00000343508.7	TSL:1	c.1301-1852T>G		intron	N/A	ENSP00000345799.3	Q7Z407-2
	CSMD3	ENST00000455883.2	TSL:1	c.1109-1852T>G		intron	N/A	ENSP00000412263.2	Q7Z407-3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64839 AN: 151746 Hom.: 14665 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.427 AC: 64883 AN: 151864 Hom.: 14672 Cov.: 32 AF XY: 0.436 AC XY: 32342 AN XY: 74232

African (AFR) AF: 0.358 AC: 14825 AN: 41444

American (AMR) AF: 0.618 AC: 9405 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1688 AN: 3466

East Asian (EAS) AF: 0.788 AC: 4056 AN: 5146

South Asian (SAS) AF: 0.489 AC: 2362 AN: 4826

European-Finnish (FIN) AF: 0.398 AC: 4208 AN: 10574

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26868 AN: 67896

Other (OTH) AF: 0.472 AC: 990 AN: 2098

Alfa AF: 0.414 Hom.: 49364

Bravo AF: 0.447

Asia WGS AF: 0.570 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.51
PhyloP100		0.86
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10505196;

hg19: chr8-113961958;