NM_001244705.2:c.1265G>T

Variant names:

• chr12-53159666-C-A
• rs1229664748
• NM_001244705.2:c.1265G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001244705.2(CSAD):​c.1265G>T​(p.Arg422Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSAD NM_001244705.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

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]

ENSG00000257808 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSAD	NM_001244705.2	c.1265G>T	p.Arg422Leu	missense_variant	Exon 16 of 17	ENST00000444623.6	NP_001231634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSAD	ENST00000444623.6	c.1265G>T	p.Arg422Leu	missense_variant	Exon 16 of 17	1	NM_001244705.2	ENSP00000415485.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	.;.;D;D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.97	D;D;.;D
M_CAP	Uncertain	0.095	D
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.3	.;.;M;M
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.5	D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.021	D;D;D;D
Polyphen		1.0	D;P;D;D
Vest4		0.76
MutPred		0.56		.;.;Gain of catalytic residue at P418 (P = 0);Gain of catalytic residue at P418 (P = 0);
MVP		0.45
MPC		0.54
ClinPred		1.0	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1229664748; hg19: chr12-53553450;