8-112244433-A-T

Variant names:

• chr8-112244433-A-T
• NM_198123.2:c.10363T>A

Variant summary

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

The NM_198123.2(CSMD3):​c.10363T>A​(p.Ser3455Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSMD3 NM_198123.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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=0.3295502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.10363T>A	p.Ser3455Thr	missense_variant	Exon 65 of 71	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.10363T>A	p.Ser3455Thr	missense_variant	Exon 65 of 71	1	NM_198123.2	ENSP00000297405.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	.;T;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D;D;D;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	2.0	.;M;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.025	D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.96	D;P;.;P
Vest4		0.55
MutPred		0.51		.;Gain of sheet (P = 0.1945);.;.;
MVP		0.70
MPC		0.22
ClinPred		0.55	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-113256662;