Genetic Variant CSMD1:p.Asn1497Thr (chr8-3219437-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1497S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CSMD1
NM_033225.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

Publications

0 publications found

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]

CSMD1 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CSMD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31385186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.4490A>C	p.Asn1497Thr	missense	Exon 29 of 70	NP_150094.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.4490A>C	p.Asn1497Thr	missense	Exon 29 of 70	ENSP00000489225.1
CSMD1	ENST00000335551.11	TSL:1	c.2930A>C	p.Asn977Thr	missense	Exon 17 of 56	ENSP00000334828.6
CSMD1	ENST00000523488.5	TSL:1	n.2023A>C		non_coding_transcript_exon	Exon 13 of 24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000150

AC:

AN:

1330064

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

651290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28286

American (AMR)

AF:

0.00

AC:

AN:

22078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20992

East Asian (EAS)

AF:

0.00

AC:

AN:

34442

South Asian (SAS)

AF:

0.00

AC:

AN:

69214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4678

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1047550

Other (OTH)

AF:

0.00

AC:

AN:

54846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.073

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0026

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

PhyloP100

2.1

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.066

Sift

Benign

0.16

Sift4G

Uncertain

0.011

Polyphen

0.071

Vest4

0.60

MutPred

0.67

Gain of glycosylation at N1498 (P = 0.0635)

MVP

0.39

ClinPred

0.91

GERP RS

3.0

Varity_R

0.19

gMVP

0.23

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over