Genetic Variant NM_007231.5:c.842T>C (chrX-116446793-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_007231.5(SLC6A14):c.842T>C(p.Val281Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,199,368 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000019 ( 0 hom. 8 hem. )

Consequence

SLC6A14
NM_007231.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53

Publications

1 publications found

Variant links:

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

SLC6A14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 8 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.842T>C	p.Val281Ala	missense	Exon 7 of 14	NP_009162.1	Q9UN76

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC6A14	ENST00000598581.3	TSL:1 MANE Select	c.842T>C	p.Val281Ala	missense	Exon 7 of 14	ENSP00000470801.1	Q9UN76
SLC6A14	ENST00000961161.1		c.842T>C	p.Val281Ala	missense	Exon 7 of 14	ENSP00000631220.1
SLC6A14	ENST00000905559.1		c.710T>C	p.Val237Ala	missense	Exon 6 of 13	ENSP00000575618.1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000566

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000273

AC:

AN:

183246

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1087978

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

353878

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26187

American (AMR)

AF:

0.00

AC:

AN:

35179

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19313

East Asian (EAS)

AF:

0.00

AC:

AN:

30123

South Asian (SAS)

AF:

0.00

AC:

AN:

53882

European-Finnish (FIN)

AF:

0.000148

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

832894

Other (OTH)

AF:

0.0000218

AC:

AN:

45773

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111390

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30635

American (AMR)

AF:

0.00

AC:

AN:

10432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.00

AC:

AN:

2661

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000566

AC:

AN:

53044

Other (OTH)

AF:

0.00

AC:

AN:

1498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000198

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.0080

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.2

PhyloP100

7.5

PrimateAI

Benign

0.36

Sift4G

Pathogenic

0.0010

Polyphen

0.44

Vest4

0.46

MutPred

0.72

Loss of stability (P = 0.041)

MVP

0.72

ClinPred

0.41

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.62

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over