8-2950251-T-A

Variant summary

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

The NM_033225.6(CSMD1):c.10294A>T(p.Asn3432Tyr) 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: CSMD1 NM_033225.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.10294A>T	p.Asn3432Tyr	missense_variant	67/70	ENST00000635120.2
LOC105377785	NR_168443.1	n.1172-58317T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.10294A>T	p.Asn3432Tyr	missense_variant	67/70	5	NM_033225.6	P4

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

Dec 07, 2023

The c.10294A>T (p.N3432Y) alteration is located in exon 67 (coding exon 67) of the CSMD1 gene. This alteration results from a A to T substitution at nucleotide position 10294, causing the asparagine (N) at amino acid position 3432 to be replaced by a tyrosine (Y). 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	Benign	0.14
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.091	T;.;.;.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T;.;T;T;.;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Uncertain	0.67	T
REVEL	Benign	0.21
Sift4G	Uncertain	0.0070	D;D;D;D;D;D
Polyphen		0.98	.;.;.;.;D;D
Vest4		0.81, 0.83, 0.81, 0.81, 0.82
MutPred		0.47		.;.;.;.;Loss of catalytic residue at N3433 (P = 0.0542);Loss of catalytic residue at N3433 (P = 0.0542);
MVP		0.46
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.46
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr8-2807773;