rs571621473

Variant names:

• chr3-14443750-C-G
• rs571621473
• NM_003043.6:c.116C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-14443750-C-G
• chr3-14443750-C-T

Variant summary

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

The NM_003043.6(SLC6A6):​c.116C>G​(p.Pro39Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. P39L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A6 NM_003043.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.85
• Publications: 0 publications found

Genes affected

SLC6A6 (HGNC:11052): (solute carrier family 6 member 6) This gene encodes a multi-pass membrane protein that is a member of a family of sodium and chloride-ion dependent transporters. The encoded protein transports taurine and beta-alanine. There is a pseudogene for this gene on chromosome 21. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

SLC6A6 Gene-Disease associations (from GenCC):

• hypotaurinemic retinal degeneration and cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

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=0.21184355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A6	NM_003043.6	c.116C>G	p.Pro39Arg	missense_variant	Exon 3 of 15	ENST00000622186.5	NP_003034.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A6	ENST00000622186.5	c.116C>G	p.Pro39Arg	missense_variant	Exon 3 of 15	1	NM_003043.6	ENSP00000480890.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T;.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.0078
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;T;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N;.;N;.
PhyloP100		5.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.6	.;.;.;N
REVEL	Benign	0.083
Sift	Benign	0.17	.;.;.;T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.029	B;.;.;.
Vest4		0.63
MutPred		0.26		Loss of catalytic residue at P38 (P = 0.0151);.;Loss of catalytic residue at P38 (P = 0.0151);Loss of catalytic residue at P38 (P = 0.0151);
MVP		0.043
ClinPred		0.82	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.34
Mutation Taster		=25/75	disease causing

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: rs571621473; hg19: chr3-14485258;