NM_007231.5:c.1074C>T

Variant names:

• chrX-116451585-C-T
• rs12720085
• NM_007231.5:c.1074C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_007231.5(SLC6A14):​c.1074C>T​(p.Ser358Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00527 in 1,207,619 control chromosomes in the GnomAD database, including 15 homozygotes. There are 2,068 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., 129 hem., cov: 23)
  • Exomes 𝑓: 0.0054 (11 hom. 1939 hem.)
• Consequence: SLC6A14 NM_007231.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.430
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant X-116451585-C-T is Benign according to our data. Variant chrX-116451585-C-T is described in ClinVar as Benign. ClinVar VariationId is 788934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.43 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.1074C>T	p.Ser358Ser	synonymous	Exon 8 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.1074C>T	p.Ser358Ser	synonymous	Exon 8 of 14	ENSP00000470801.1	Q9UN76
	SLC6A14	ENST00000961161.1		c.1074C>T	p.Ser358Ser	synonymous	Exon 8 of 14	ENSP00000631220.1
	SLC6A14	ENST00000905559.1		c.942C>T	p.Ser314Ser	synonymous	Exon 7 of 13	ENSP00000575618.1

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 465 AN: 110856 Hom.: 4 Cov.: 23

Gnomad AFR AF: 0.000754

Gnomad AMI AF: 0.0706

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.000379

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00302

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00531

Gnomad OTH AF: 0.00201

GnomAD2 exomes AF: 0.00464 AC: 849 AN: 182943 AF XY: 0.00488

Gnomad AFR exome AF: 0.000836

Gnomad AMR exome AF: 0.00336

Gnomad ASJ exome AF: 0.00201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0121

Gnomad NFE exome AF: 0.00544

Gnomad OTH exome AF: 0.00730

GnomAD4 exome AF: 0.00538 AC: 5898 AN: 1096718 Hom.: 11 Cov.: 29 AF XY: 0.00535 AC XY: 1939 AN XY: 362168

African (AFR) AF: 0.000986 AC: 26 AN: 26376

American (AMR) AF: 0.00315 AC: 111 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.00181 AC: 35 AN: 19370

East Asian (EAS) AF: 0.00 AC: 0 AN: 30175

South Asian (SAS) AF: 0.00394 AC: 213 AN: 54092

European-Finnish (FIN) AF: 0.0130 AC: 526 AN: 40514

Middle Eastern (MID) AF: 0.00170 AC: 7 AN: 4127

European-Non Finnish (NFE) AF: 0.00564 AC: 4741 AN: 840837

Other (OTH) AF: 0.00519 AC: 239 AN: 46039

GnomAD4 genome AF: 0.00420 AC: 466 AN: 110901 Hom.: 4 Cov.: 23 AF XY: 0.00389 AC XY: 129 AN XY: 33135

African (AFR) AF: 0.000752 AC: 23 AN: 30574

American (AMR) AF: 0.00290 AC: 30 AN: 10345

Ashkenazi Jewish (ASJ) AF: 0.000379 AC: 1 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3529

South Asian (SAS) AF: 0.00303 AC: 8 AN: 2639

European-Finnish (FIN) AF: 0.0124 AC: 72 AN: 5817

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.00531 AC: 281 AN: 52952

Other (OTH) AF: 0.00199 AC: 3 AN: 1511

Alfa AF: 0.00458 Hom.: 41

Bravo AF: 0.00354

EpiCase AF: 0.00493

EpiControl AF: 0.00457

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	6.3
DANN	Benign	0.64
PhyloP100		-0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12720085; hg19: chrX-115582750;