chrX-116441070-G-A

Variant names:

• chrX-116441070-G-A
• NM_007231.5:c.319G>A

Variant summary

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

The NM_007231.5(SLC6A14):​c.319G>A​(p.Val107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC6A14 NM_007231.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.430
• Publications: 0 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: 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=0.12550321).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007231.5. 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
	SLC6A14	NM_007231.5	MANE Select	c.319G>A	p.Val107Ile	missense	Exon 3 of 14	NP_009162.1	Q9UN76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A14	ENST00000598581.3	TSL:1 MANE Select	c.319G>A	p.Val107Ile	missense	Exon 3 of 14	ENSP00000470801.1	Q9UN76
	SLC6A14	ENST00000961161.1		c.319G>A	p.Val107Ile	missense	Exon 3 of 14	ENSP00000631220.1
	SLC6A14	ENST00000961159.1		c.319G>A	p.Val107Ile	missense	Exon 3 of 13	ENSP00000631218.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.58	N
PhyloP100		0.43
PrimateAI	Benign	0.35	T
Sift4G	Benign	0.32	T
Polyphen		0.0060	B
Vest4		0.15
MutPred		0.58		Gain of catalytic residue at V107 (P = 0.0739)
MVP		0.15
ClinPred		0.15	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.61
Mutation Taster		=99/1	polymorphism

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

hg19: chrX-115572238;