8-2950314-G-C

Variant summary

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

The NM_033225.6(CSMD1):c.10231C>G(p.Leu3411Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CSMD1 NM_033225.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

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=0.40285757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.10231C>G	p.Leu3411Val	missense_variant	67/70	ENST00000635120.2
LOC105377785	NR_168443.1	n.1172-58254G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.10231C>G	p.Leu3411Val	missense_variant	67/70	5	NM_033225.6	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461012 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726808

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Mar 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.082	T;.;.;T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D;.;D;D;.;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.40	T;T;T;T;T;T
MetaSVM	Benign	-0.44	T
MutationTaster	Benign	0.78	D;D;D;D
PrimateAI	Uncertain	0.61	T
REVEL	Benign	0.17
Sift4G	Uncertain	0.0040	D;D;D;D;D;D
Polyphen		1.0	.;.;.;.;D;D
Vest4		0.44, 0.43, 0.47, 0.48, 0.48
MutPred		0.62		.;.;.;.;Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);
MVP		0.28
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr8-2807836;