chr3-14454654-G-A

Variant names:

• chr3-14454654-G-A
• rs11128699
• NM_003043.6:c.600-3296G>A

Variant summary

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

The NM_003043.6(SLC6A6):​c.600-3296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,038 control chromosomes in the GnomAD database, including 14,480 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 0.43 (14480 hom., cov: 33)
• Consequence: SLC6A6 NM_003043.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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: LIMITED Submitted by: 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 = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A6	NM_003043.6	c.600-3296G>A		intron_variant	Intron 5 of 14	ENST00000622186.5	NP_003034.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A6	ENST00000622186.5	c.600-3296G>A		intron_variant	Intron 5 of 14	1	NM_003043.6	ENSP00000480890.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65484 AN: 151920 Hom.: 14462 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.431 AC: 65535 AN: 152038 Hom.: 14480 Cov.: 33 AF XY: 0.429 AC XY: 31865 AN XY: 74324

African (AFR) AF: 0.513 AC: 21265 AN: 41474

American (AMR) AF: 0.328 AC: 5016 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1410 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2048 AN: 5170

South Asian (SAS) AF: 0.476 AC: 2294 AN: 4824

European-Finnish (FIN) AF: 0.341 AC: 3604 AN: 10558

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28499 AN: 67954

Other (OTH) AF: 0.433 AC: 914 AN: 2112

Alfa AF: 0.417 Hom.: 39020

Bravo AF: 0.431

Asia WGS AF: 0.427 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.014
DANN	Benign	0.55
PhyloP100		-1.2
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: rs11128699; hg19: chr3-14496162;