NM_001244705.2:c.1256C>G

Variant names:

• chr12-53159675-G-C
• rs140401098
• NM_001244705.2:c.1256C>G

Variant summary

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

The NM_001244705.2(CSAD):​c.1256C>G​(p.Pro419Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000114 in 1,611,578 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P419A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CSAD NM_001244705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.59
• Publications: 6 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.

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.1256C>G	p.Pro419Arg	missense	Exon 16 of 17	NP_001231634.1	Q9Y600-1
	CSAD	NM_015989.5		c.1337C>G	p.Pro446Arg	missense	Exon 16 of 17	NP_057073.4
	CSAD	NM_001244706.2		c.557C>G	p.Pro186Arg	missense	Exon 7 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.1256C>G	p.Pro419Arg	missense	Exon 16 of 17	ENSP00000415485.1	Q9Y600-1
	CSAD	ENST00000267085.8	TSL:1	c.1337C>G	p.Pro446Arg	missense	Exon 16 of 17	ENSP00000267085.3	Q9Y600-3
	CSAD	ENST00000453446.6	TSL:1	c.1256C>G	p.Pro419Arg	missense	Exon 15 of 16	ENSP00000410648.2	Q9Y600-1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000147 AC: 36 AN: 245400 AF XY: 0.000189

Gnomad AFR exome AF: 0.0000642

Gnomad AMR exome AF: 0.000148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000902

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000112 AC: 163 AN: 1459276 Hom.: 0 Cov.: 31 AF XY: 0.000145 AC XY: 105 AN XY: 725552

African (AFR) AF: 0.0000598 AC: 2 AN: 33462

American (AMR) AF: 0.000226 AC: 10 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000468 AC: 40 AN: 85502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5764

European-Non Finnish (NFE) AF: 0.0000828 AC: 92 AN: 1110918

Other (OTH) AF: 0.000133 AC: 8 AN: 60314

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74472

African (AFR) AF: 0.0000241 AC: 1 AN: 41546

American (AMR) AF: 0.000457 AC: 7 AN: 15304

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

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

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000142 Hom.: 1

Bravo AF: 0.000200

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000198 AC: 24

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.056	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.42		Gain of catalytic residue at P418 (P = 0.0055)
MVP		0.55
MPC		0.61
ClinPred		0.65	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.60
Mutation Taster		=7/93	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs140401098; hg19: chr12-53553459;