rs777459005

Variant names:

• chr8-2949338-G-A
• rs777459005
• NM_033225.6:c.10363C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-2949338-G-A
• chr8-2949338-G-T

Variant summary

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

The NM_033225.6(CSMD1):​c.10363C>T​(p.His3455Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CSMD1 NM_033225.6 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26537693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.10363C>T	p.His3455Tyr	missense_variant	Exon 68 of 70	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.10363C>T	p.His3455Tyr	missense_variant	Exon 68 of 70	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455850 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724484

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;.;.;.;T;T
Eigen	Benign	0.054
Eigen_PC	Benign	0.057
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.72	T;.;T;T;.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Benign	-0.75	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	.;N;.;.;N;.
REVEL	Benign	0.093
Sift	Uncertain	0.027	.;D;.;.;D;.
Sift4G	Uncertain	0.014	D;D;D;D;D;D
Polyphen		0.84	.;.;.;.;P;P
Vest4		0.44, 0.44, 0.41, 0.42
MutPred		0.37		.;.;.;.;Loss of disorder (P = 0.058);Loss of disorder (P = 0.058);
MVP		0.51
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.19
gMVP		0.49

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: rs777459005; hg19: chr8-2806860;