X-116436924-A-T

Variant names:

• chrX-116436924-A-T
• rs2312054
• NM_007231.5:c.48+167A>T

Variant summary

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

The NM_007231.5(SLC6A14):​c.48+167A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 111,030 control chromosomes in the GnomAD database, including 1,772 homozygotes. There are 6,411 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 0.20 (1772 hom., 6411 hem., cov: 22)
• Consequence: SLC6A14 NM_007231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A14	NM_007231.5	c.48+167A>T		intron_variant	Intron 1 of 13	ENST00000598581.3	NP_009162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A14	ENST00000598581.3	c.48+167A>T		intron_variant	Intron 1 of 13	1	NM_007231.5	ENSP00000470801.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 21999 AN: 110978 Hom.: 1771 Cov.: 22

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.198 AC: 22021 AN: 111030 Hom.: 1772 Cov.: 22 AF XY: 0.193 AC XY: 6411 AN XY: 33282

African (AFR) AF: 0.143 AC: 4376 AN: 30573

American (AMR) AF: 0.261 AC: 2733 AN: 10473

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 397 AN: 2630

East Asian (EAS) AF: 0.0381 AC: 134 AN: 3513

South Asian (SAS) AF: 0.126 AC: 333 AN: 2650

European-Finnish (FIN) AF: 0.205 AC: 1225 AN: 5973

Middle Eastern (MID) AF: 0.180 AC: 39 AN: 217

European-Non Finnish (NFE) AF: 0.234 AC: 12372 AN: 52811

Other (OTH) AF: 0.197 AC: 298 AN: 1513

Alfa AF: 0.217 Hom.: 1299

Bravo AF: 0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.62
PhyloP100		0.77
PromoterAI		0.0090	Neutral

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: rs2312054; hg19: chrX-115568092;