8-112228859-T-C

Variant names:

• chr8-112228859-T-C
• rs1592624
• NM_198123.2:c.10861A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198123.2(CSMD3):​c.10861A>G​(p.Asn3621Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N3621H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSMD3 NM_198123.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32543898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.10861A>G	p.Asn3621Asp	missense_variant	Exon 70 of 71	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.10861A>G	p.Asn3621Asp	missense_variant	Exon 70 of 71	1	NM_198123.2	ENSP00000297405.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Benign	0.76
DEOGEN2	Benign	0.040	.;T;T;.
Eigen	Benign	0.064
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.074
Sift	Benign	0.65	T;T;T;T
Sift4G	Benign	0.50	T;T;T;T
Polyphen		0.87	P;B;.;B
Vest4		0.34
MutPred		0.10		.;Gain of phosphorylation at S3619 (P = 0.1461);.;.;
MVP		0.45
MPC		0.18
ClinPred		0.50	D
GERP RS		5.6
Varity_R		0.20
gMVP		0.27

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

LitVar

Other links and lift over

dbSNP: rs1592624; hg19: chr8-113241088;