3-14459236-C-T

Variant names:

• chr3-14459236-C-T
• rs3773176
• NM_003043.6:c.732+1154C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003043.6(SLC6A6):​c.732+1154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,978 control chromosomes in the GnomAD database, including 25,150 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (25150 hom., cov: 32)
• Consequence: SLC6A6 NM_003043.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 5 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: MODERATE, LIMITED Submitted by: PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003043.6. 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
	SLC6A6	NM_003043.6	MANE Select	c.732+1154C>T		intron	N/A	NP_003034.2	P31641-1
	SLC6A6	NM_001134367.3		c.1035+1154C>T		intron	N/A	NP_001127839.2	Q59GD7
	SLC6A6	NR_103507.3		n.1027+1154C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A6	ENST00000622186.5	TSL:1 MANE Select	c.732+1154C>T		intron	N/A	ENSP00000480890.1	P31641-1
	SLC6A6	ENST00000613060.4	TSL:1	c.1035+1154C>T		intron	N/A	ENSP00000481625.1	A0A087WY96
	SLC6A6	ENST00000855618.1		c.732+1154C>T		intron	N/A	ENSP00000525677.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83157 AN: 151860 Hom.: 25098 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.548 AC: 83254 AN: 151978 Hom.: 25150 Cov.: 32 AF XY: 0.544 AC XY: 40389 AN XY: 74286

African (AFR) AF: 0.820 AC: 33991 AN: 41462

American (AMR) AF: 0.395 AC: 6026 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1588 AN: 3470

East Asian (EAS) AF: 0.445 AC: 2292 AN: 5150

South Asian (SAS) AF: 0.584 AC: 2810 AN: 4812

European-Finnish (FIN) AF: 0.370 AC: 3904 AN: 10558

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30997 AN: 67946

Other (OTH) AF: 0.537 AC: 1130 AN: 2106

Alfa AF: 0.477 Hom.: 22522

Bravo AF: 0.559

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.79
DANN	Benign	0.45
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs3773176; hg19: chr3-14500744;