chr12-53158588-C-T

Variant names:

• chr12-53158588-C-T
• rs769957361
• NM_001244705.2:c.1405G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001244705.2(CSAD):​c.1405G>A​(p.Val469Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. V469L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSAD NM_001244705.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSAD	NM_001244705.2	MANE Select	c.1405G>A	p.Val469Met	missense	Exon 17 of 17	NP_001231634.1	Q9Y600-1
	CSAD	NM_015989.5		c.1486G>A	p.Val496Met	missense	Exon 17 of 17	NP_057073.4
	CSAD	NM_001244706.2		c.706G>A	p.Val236Met	missense	Exon 8 of 8	NP_001231635.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSAD	ENST00000444623.6	TSL:1 MANE Select	c.1405G>A	p.Val469Met	missense	Exon 17 of 17	ENSP00000415485.1	Q9Y600-1
	CSAD	ENST00000267085.8	TSL:1	c.1486G>A	p.Val496Met	missense	Exon 17 of 17	ENSP00000267085.3	Q9Y600-3
	CSAD	ENST00000453446.6	TSL:1	c.1405G>A	p.Val469Met	missense	Exon 16 of 16	ENSP00000410648.2	Q9Y600-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		1.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.52		Gain of catalytic residue at F464 (P = 0.0067)
MVP		0.53
MPC		0.62
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.54
gMVP		0.68
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs769957361; hg19: chr12-53552372;