NM_001244705.2:c.1135C>T

Variant names:

• chr12-53160151-G-A
• rs1004198719
• NM_001244705.2:c.1135C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001244705.2(CSAD):​c.1135C>T​(p.Arg379Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CSAD NM_001244705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.711
• Publications: 2 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]

ENSG00000257808 (HGNC:58448):

ACMG classification

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=0.15162241).

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.1135C>T	p.Arg379Trp	missense	Exon 14 of 17	NP_001231634.1	Q9Y600-1
	CSAD	NM_015989.5		c.1216C>T	p.Arg406Trp	missense	Exon 14 of 17	NP_057073.4
	CSAD	NM_001244706.2		c.436C>T	p.Arg146Trp	missense	Exon 5 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.1135C>T	p.Arg379Trp	missense	Exon 14 of 17	ENSP00000415485.1	Q9Y600-1
	CSAD	ENST00000267085.8	TSL:1	c.1216C>T	p.Arg406Trp	missense	Exon 14 of 17	ENSP00000267085.3	Q9Y600-3
	CSAD	ENST00000453446.6	TSL:1	c.1135C>T	p.Arg379Trp	missense	Exon 13 of 16	ENSP00000410648.2	Q9Y600-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461328 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727000

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74332

African (AFR) AF: 0.0000724 AC: 3 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.71
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.16
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.020	D
Polyphen		0.0050	B
Vest4		0.30
MutPred		0.49		Gain of catalytic residue at L377 (P = 0)
MVP		0.39
MPC		0.14
ClinPred		0.91	D
GERP RS		3.8
Varity_R		0.16
gMVP		0.45
Mutation Taster		=63/37	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: rs1004198719; hg19: chr12-53553935; COSMIC: COSV57244760; COSMIC: COSV57244760;