rs1592624

Variant names:

• chr8-112228859-T-A
• rs1592624
• NM_198123.2:c.10861A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-112228859-T-A
• chr8-112228859-T-C
• chr8-112228859-T-G

Variant summary

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

The NM_198123.2(CSMD3):​c.10861A>T​(p.Asn3621Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N3621H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSMD3 NM_198123.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

Genes affected

CSMD3 (HGNC:19291): (CUB and Sushi multiple domains 3) Predicted to be involved in regulation of dendrite development. Predicted to be located in plasma 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
CSMD3	NM_198123.2	c.10861A>T	p.Asn3621Tyr	missense_variant	Exon 70 of 71	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.10861A>T	p.Asn3621Tyr	missense_variant	Exon 70 of 71	1	NM_198123.2	ENSP00000297405.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1425568 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 711594

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	.;T;T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	.;L;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.98	D;D;.;D
Vest4		0.55
MutPred		0.096		.;Gain of phosphorylation at N3621 (P = 0.0381);.;.;
MVP		0.17
MPC		0.54
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.12
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1592624; hg19: chr8-113241088;