X-116459133-C-G

Variant names:

• chrX-116459133-C-G
• rs2011162
• NM_007231.5:c.*178C>G

Variant summary

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

The NM_007231.5(SLC6A14):​c.*178C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 360,017 control chromosomes in the GnomAD database, including 39,818 homozygotes. There are 57,455 hemizygotes in GnomAD. 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 0.50 (10585 hom., 15426 hem., cov: 21)
  • Exomes 𝑓: 0.57 (29233 hom. 42029 hem.)
• Consequence: SLC6A14 NM_007231.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 16 publications found

Genes affected

SLC6A14 (HGNC:11047): (solute carrier family 6 member 14) This gene encodes a member of the solute carrier family 6. Members of this family are sodium and chloride dependent neurotransmitter transporters. The encoded protein transports both neutral and cationic amino acids. This protein may also function as a beta-alanine carrier. Mutations in this gene may be associated with X-linked obesity. A pseudogene of this gene is found on chromosome X.[provided by RefSeq, May 2010]

SLC6A14 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A14	NM_007231.5	c.*178C>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000598581.3	NP_009162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A14	ENST00000598581.3	c.*178C>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_007231.5	ENSP00000470801.1
SLC6A14	ENST00000463626.1	n.*191C>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 53879 AN: 108736 Hom.: 10592 Cov.: 21

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.524

GnomAD4 exome AF: 0.571 AC: 143522 AN: 251235 Hom.: 29233 Cov.: 4 AF XY: 0.592 AC XY: 42029 AN XY: 70969

African (AFR) AF: 0.262 AC: 1769 AN: 6754

American (AMR) AF: 0.733 AC: 6004 AN: 8187

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 5224 AN: 7976

East Asian (EAS) AF: 0.465 AC: 8735 AN: 18794

South Asian (SAS) AF: 0.434 AC: 4228 AN: 9737

European-Finnish (FIN) AF: 0.560 AC: 13802 AN: 24628

Middle Eastern (MID) AF: 0.575 AC: 638 AN: 1109

European-Non Finnish (NFE) AF: 0.595 AC: 94244 AN: 158286

Other (OTH) AF: 0.563 AC: 8878 AN: 15764

GnomAD4 genome AF: 0.495 AC: 53893 AN: 108782 Hom.: 10585 Cov.: 21 AF XY: 0.493 AC XY: 15426 AN XY: 31268

African (AFR) AF: 0.257 AC: 7738 AN: 30104

American (AMR) AF: 0.678 AC: 6800 AN: 10036

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 1734 AN: 2625

East Asian (EAS) AF: 0.459 AC: 1562 AN: 3406

South Asian (SAS) AF: 0.375 AC: 952 AN: 2537

European-Finnish (FIN) AF: 0.530 AC: 2940 AN: 5550

Middle Eastern (MID) AF: 0.555 AC: 116 AN: 209

European-Non Finnish (NFE) AF: 0.590 AC: 30749 AN: 52160

Other (OTH) AF: 0.524 AC: 779 AN: 1486

Alfa AF: 0.528 Hom.: 3786

Bravo AF: 0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.96
DANN	Benign	0.43
PhyloP100		0.23

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: rs2011162; hg19: chrX-115590299;