rs10505170

Variant names:

• chr8-112631533-A-T
• rs10505170
• NM_198123.2:c.3715+5284T>A

Variant summary

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

The NM_198123.2(CSMD3):​c.3715+5284T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,980 control chromosomes in the GnomAD database, including 1,921 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 0.14 (1921 hom., cov: 33)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.3715+5284T>A		intron_variant	Intron 22 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.3715+5284T>A		intron_variant	Intron 22 of 70	1	NM_198123.2	ENSP00000297405.5
CSMD3	ENST00000343508.7	c.3595+5284T>A		intron_variant	Intron 23 of 71	1		ENSP00000345799.3
CSMD3	ENST00000455883.2	c.3403+5284T>A		intron_variant	Intron 21 of 68	1		ENSP00000412263.2
CSMD3	ENST00000339701.7	c.1735+5284T>A		intron_variant	Intron 9 of 55	1		ENSP00000341558.3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21026 AN: 151860 Hom.: 1917 Cov.: 33

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.138 AC: 21036 AN: 151980 Hom.: 1921 Cov.: 33 AF XY: 0.144 AC XY: 10672 AN XY: 74282

African (AFR) AF: 0.0312 AC: 1295 AN: 41518

American (AMR) AF: 0.210 AC: 3194 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3464

East Asian (EAS) AF: 0.133 AC: 686 AN: 5164

South Asian (SAS) AF: 0.101 AC: 486 AN: 4824

European-Finnish (FIN) AF: 0.262 AC: 2760 AN: 10552

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11633 AN: 67924

Other (OTH) AF: 0.141 AC: 296 AN: 2104

Alfa AF: 0.153 Hom.: 256

Bravo AF: 0.130

Asia WGS AF: 0.0930 AC: 324 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.54
PhyloP100		0.91
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: rs10505170; hg19: chr8-113643762;