rs3824271

Positions:

• chr8-3107722-T-A
• chr8-3107722-T-C

Variant summary

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

The NM_033225.6(CSMD1):​c.6831A>T​(p.Glu2277Asp) 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. 13/19 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSMD1 NM_033225.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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]

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=0.23200837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.6831A>T	p.Glu2277Asp	missense_variant	45/70	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.6831A>T	p.Glu2277Asp	missense_variant	45/70	5	NM_033225.6	ENSP00000489225	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1423674 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 709780

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T;.;.;.;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.77	T;.;T;T;.;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationTaster	Benign	0.42	P;P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	.;N;.;.;N;.
REVEL	Benign	0.14
Sift	Uncertain	0.014	.;D;.;.;T;.
Sift4G	Benign	0.078	T;T;T;T;T;T
Polyphen		0.99	.;.;.;.;D;D
Vest4		0.23, 0.22, 0.20, 0.18, 0.23
MutPred		0.57		.;Loss of disorder (P = 0.2207);Loss of disorder (P = 0.2207);.;Loss of disorder (P = 0.2207);Loss of disorder (P = 0.2207);
MVP		0.58
ClinPred		0.52	D
GERP RS		-1.3
Varity_R		0.086
gMVP		0.25

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: rs3824271; hg19: chr8-2965244;