rs28455997

Variant names:

• chr8-3219437-T-A
• rs28455997
• NM_033225.6:c.4490A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-3219437-T-A
• chr8-3219437-T-C
• chr8-3219437-T-G

Variant summary

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

The NM_033225.6(CSMD1):​c.4490A>T​(p.Asn1497Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000135 in 1,482,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CSMD1 NM_033225.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.4490A>T	p.Asn1497Ile	missense_variant	Exon 29 of 70	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.4490A>T	p.Asn1497Ile	missense_variant	Exon 29 of 70	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1330064 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 651290

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: 0.0000144

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74300

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;.;.;.;T;T
Eigen	Benign	0.022
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;.;D;D;.;D
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.1	.;D;.;.;D;.
REVEL	Benign	0.12
Sift	Uncertain	0.0080	.;D;.;.;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D
Polyphen		0.56	.;.;.;.;P;P
Vest4		0.88, 0.88, 0.91, 0.87, 0.86
MutPred		0.74		.;Gain of ubiquitination at K1495 (P = 0.1008);Gain of ubiquitination at K1495 (P = 0.1008);.;Gain of ubiquitination at K1495 (P = 0.1008);Gain of ubiquitination at K1495 (P = 0.1008);
MVP		0.40
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.71
gMVP		0.42

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: rs28455997; hg19: chr8-3076959;