8-112231559-C-T

Position:

• chr8-112231559-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198123.2(CSMD3):​c.10814G>A​(p.Gly3605Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSMD3 NM_198123.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD3	NM_198123.2	c.10814G>A	p.Gly3605Asp	missense_variant	69/71	ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10	c.10814G>A	p.Gly3605Asp	missense_variant	69/71	1	NM_198123.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.10814G>A (p.G3605D) alteration is located in exon 69 (coding exon 69) of the CSMD3 gene. This alteration results from a G to A substitution at nucleotide position 10814, causing the glycine (G) at amino acid position 3605 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;T;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	.;M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.3	D;D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.48	P;D;.;D
Vest4		0.64
MutPred		0.45		.;Gain of catalytic residue at G3605 (P = 0.0885);.;.;
MVP		0.41
MPC		0.47
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.69
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-113243788; COSMIC: COSV99822068;