dbSNP rs774684695: CSAD:p.Val440Leu (chr12-53158675-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001244705.2(CSAD):c.1318G>T(p.Val440Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V440M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CSAD
NM_001244705.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.599

Publications

0 publications found

Variant links:

Genes affected

CSAD (HGNC:18966): (cysteine sulfinic acid decarboxylase) This gene encodes a member of the group 2 decarboxylase family. A similar protein in rodents plays a role in multiple biological processes as the rate-limiting enzyme in taurine biosynthesis, catalyzing the decarboxylation of cysteinesulfinate to hypotaurine. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

CSAD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077459246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244705.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSAD	NM_001244705.2	MANE Select	c.1318G>T	p.Val440Leu	missense	Exon 17 of 17	NP_001231634.1	Q9Y600-1
CSAD	NM_015989.5		c.1399G>T	p.Val467Leu	missense	Exon 17 of 17	NP_057073.4
CSAD	NM_001244706.2		c.619G>T	p.Val207Leu	missense	Exon 8 of 8	NP_001231635.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSAD	ENST00000444623.6	TSL:1 MANE Select	c.1318G>T	p.Val440Leu	missense	Exon 17 of 17	ENSP00000415485.1	Q9Y600-1
CSAD	ENST00000267085.8	TSL:1	c.1399G>T	p.Val467Leu	missense	Exon 17 of 17	ENSP00000267085.3	Q9Y600-3
CSAD	ENST00000453446.6	TSL:1	c.1318G>T	p.Val440Leu	missense	Exon 16 of 16	ENSP00000410648.2	Q9Y600-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

249038

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111896

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.9

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.31

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.85

M_CAP

Benign

0.012

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-0.60

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

REVEL

Benign

0.029

Sift

Benign

0.31

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.031

MutPred

0.39

Gain of catalytic residue at K436 (P = 0.0112)

MVP

0.15

MPC

0.14

ClinPred

0.062

GERP RS

-2.0

Varity_R

0.14

gMVP

0.39

Mutation Taster

=77/23

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over