8-3219437-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033225.6(CSMD1):​c.4490A>C​(p.Asn1497Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,330,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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 š‘“: 0.0000015 ( 0 hom. )

Consequence

CSMD1
NM_033225.6 missense

Scores

5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.31385186).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSMD1NM_033225.6 linkc.4490A>C p.Asn1497Thr missense_variant Exon 29 of 70 ENST00000635120.2 NP_150094.5 Q96PZ7-1Q59FF8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSMD1ENST00000635120.2 linkc.4490A>C p.Asn1497Thr missense_variant Exon 29 of 70 5 NM_033225.6 ENSP00000489225.1 Q96PZ7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000150
AC:
2
AN:
1330064
Hom.:
0
Cov.:
29
AF XY:
0.00000154
AC XY:
1
AN XY:
651290
show subpopulations
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:
0.00000191
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
Benign
0.15
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T;.;.;.;T;T
Eigen
Benign
-0.073
Eigen_PC
Benign
0.015
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D;.;D;D;.;D
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.31
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-2.6
.;D;.;.;N;.
REVEL
Benign
0.066
Sift
Benign
0.16
.;T;.;.;D;.
Sift4G
Uncertain
0.011
D;D;D;D;D;D
Polyphen
0.071
.;.;.;.;B;B
Vest4
0.60, 0.61, 0.63, 0.68, 0.55
MutPred
0.67
.;Gain of glycosylation at N1498 (P = 0.0635);Gain of glycosylation at N1498 (P = 0.0635);.;Gain of glycosylation at N1498 (P = 0.0635);Gain of glycosylation at N1498 (P = 0.0635);
MVP
0.39
ClinPred
0.91
D
GERP RS
3.0
Varity_R
0.19
gMVP
0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-3076959; API