chr12-53158546-G-A

Position:

• chr12-53158546-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001244705.2(CSAD):​c.1447C>T​(p.Leu483Phe) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSAD NM_001244705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41125077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSAD	NM_001244705.2	c.1447C>T	p.Leu483Phe	missense_variant	17/17	ENST00000444623.6	NP_001231634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSAD	ENST00000444623.6	c.1447C>T	p.Leu483Phe	missense_variant	17/17	1	NM_001244705.2	ENSP00000415485.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2021

The c.1528C>T (p.L510F) alteration is located in exon 17 (coding exon 16) of the CSAD gene. This alteration results from a C to T substitution at nucleotide position 1528, causing the leucine (L) at amino acid position 510 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	.;.;D;D
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;.;D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Uncertain	-0.086	T
MutationAssessor	Uncertain	2.8	.;.;M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;T;D;D
Sift4G	Uncertain	0.041	D;T;D;D
Polyphen		1.0	D;P;D;D
Vest4		0.48
MutPred		0.57		.;.;Gain of catalytic residue at M479 (P = 0.0283);Gain of catalytic residue at M479 (P = 0.0283);
MVP		0.61
MPC		0.64
ClinPred		0.98	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.67
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs1938827495; hg19: chr12-53552330;