rs746303001

Variant names:

• chr8-2942578-A-G
• rs746303001
• NM_033225.6:c.10429T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-2942578-A-G
• chr8-2942578-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033225.6(CSMD1):​c.10429T>C​(p.Ser3477Pro) 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. 14/19 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: CSMD1 NM_033225.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105377785 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114604026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.10429T>C	p.Ser3477Pro	missense_variant	Exon 69 of 70	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.10429T>C	p.Ser3477Pro	missense_variant	Exon 69 of 70	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.72
DEOGEN2	Benign	0.022	T;.;.;T;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.62	T;.;T;T;.;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	.;N;.;.;N;.
REVEL	Benign	0.14
Sift	Benign	0.30	.;T;.;.;T;.
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		0.0040	.;.;.;.;B;B
Vest4		0.28, 0.34, 0.23, 0.20, 0.19
MutPred		0.18		.;.;.;.;Loss of phosphorylation at S3478 (P = 0.0349);Loss of phosphorylation at S3478 (P = 0.0349);
MVP		0.22
ClinPred		0.50	D
GERP RS		3.2
Varity_R		0.25
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs746303001; hg19: chr8-2800100;