NM_012244.4:c.1499G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_012244.4(SLC7A8):c.1499G>A(p.Arg500Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

SLC7A8
NM_012244.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.74

Publications

1 publications found

Variant links:

Genes affected

SLC7A8 (HGNC:11066): (solute carrier family 7 member 8) Enables several functions, including neutral amino acid transmembrane transporter activity; thyroid hormone transmembrane transporter activity; and toxin transmembrane transporter activity. Involved in L-alanine import across plasma membrane; L-leucine import across plasma membrane; and thyroid hormone transport. Located in plasma membrane. Part of basolateral plasma membrane and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A8 links:

ENSG00000295888 (HGNC:):

ENSG00000295888 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026576042).

BP6

Variant 14-23127286-C-T is Benign according to our data. Variant chr14-23127286-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2457382.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012244.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A8	NM_012244.4	MANE Select	c.1499G>A	p.Arg500Gln	missense	Exon 11 of 11	NP_036376.2
SLC7A8	NM_001267036.1		c.1184G>A	p.Arg395Gln	missense	Exon 9 of 9	NP_001253965.1	Q9UHI5-4
SLC7A8	NM_182728.3		c.890G>A	p.Arg297Gln	missense	Exon 9 of 9	NP_877392.1	Q9UHI5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A8	ENST00000316902.12	TSL:1 MANE Select	c.1499G>A	p.Arg500Gln	missense	Exon 11 of 11	ENSP00000320378.7	Q9UHI5-1
SLC7A8	ENST00000453702.5	TSL:1	c.890G>A	p.Arg297Gln	missense	Exon 9 of 9	ENSP00000391577.1	Q9UHI5-2
SLC7A8	ENST00000469263.5	TSL:1	c.846G>A	p.Ala282Ala	synonymous	Exon 6 of 6	ENSP00000435114.1	E9PLV9

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

250832

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

1111978

Other (OTH)

AF:

0.000215

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000985

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41520

American (AMR)

AF:

0.000588

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68006

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000675

Hom.:

Bravo

AF:

0.000246

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.061

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.24

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.19

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.32

M_CAP

Benign

0.0079

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.0

PhyloP100

-1.7

PrimateAI

Benign

0.20

PROVEAN

Benign

0.60

REVEL

Benign

0.22

Sift

Benign

0.62

Sift4G

Benign

0.54

Polyphen

0.0060

Vest4

0.046

MutPred

0.21

Gain of disorder (P = 0.1386)

MVP

0.32

MPC

0.17

ClinPred

0.026

GERP RS

-7.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.017

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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