8-112234411-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198123.2(CSMD3):​c.10694C>A​(p.Ala3565Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Consequence

CSMD3
NM_198123.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10688445).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CSMD3NM_198123.2 linkuse as main transcriptc.10694C>A p.Ala3565Asp missense_variant 68/71 ENST00000297405.10 NP_937756.1 Q7Z407-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CSMD3ENST00000297405.10 linkuse as main transcriptc.10694C>A p.Ala3565Asp missense_variant 68/711 NM_198123.2 ENSP00000297405.5 Q7Z407-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152022
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
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
Cov.:
30
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152022
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74250
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
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
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 01, 2024The c.10694C>A (p.A3565D) alteration is located in exon 68 (coding exon 68) of the CSMD3 gene. This alteration results from a C to A substitution at nucleotide position 10694, causing the alanine (A) at amino acid position 3565 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.041
.;T;T;.
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.41
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.75
T;T;T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.8
N;N;N;N
REVEL
Benign
0.10
Sift
Benign
0.13
T;T;T;T
Sift4G
Benign
0.14
T;T;T;T
Polyphen
0.0030
B;B;.;B
Vest4
0.48
MutPred
0.48
.;Loss of MoRF binding (P = 0.0516);.;.;
MVP
0.24
MPC
0.25
ClinPred
0.26
T
GERP RS
2.4
Varity_R
0.21
gMVP
0.62

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1301822307; hg19: chr8-113246640; COSMIC: COSV52099455; API