Genetic Variant NM_012244.4:c.1159C>A (chr14-23129754-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_012244.4(SLC7A8):c.1159C>A(p.Leu387Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

SLC7A8
NM_012244.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.07

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1159C>A	p.Leu387Ile	missense	Exon 9 of 11	NP_036376.2
SLC7A8	NM_001267036.1		c.844C>A	p.Leu282Ile	missense	Exon 7 of 9	NP_001253965.1	Q9UHI5-4
SLC7A8	NM_182728.3		c.550C>A	p.Leu184Ile	missense	Exon 7 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.1159C>A	p.Leu387Ile	missense	Exon 9 of 11	ENSP00000320378.7	Q9UHI5-1
SLC7A8	ENST00000453702.5	TSL:1	c.550C>A	p.Leu184Ile	missense	Exon 7 of 9	ENSP00000391577.1	Q9UHI5-2
SLC7A8	ENST00000469263.5	TSL:1	c.789-2411C>A		intron	N/A	ENSP00000435114.1	E9PLV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251434

AF XY:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000540

AC:

AN:

1111988

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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

Cov.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

0.047

MutationAssessor

Uncertain

2.5

PhyloP100

8.1

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.7

REVEL

Pathogenic

0.79

Sift

Uncertain

0.023

Sift4G

Uncertain

0.037

Polyphen

0.99

Vest4

0.67

MutPred

0.57

Loss of catalytic residue at L387 (P = 0.0443)

MVP

0.82

MPC

0.60

ClinPred

0.82

GERP RS

5.9

Varity_R

0.40

gMVP

0.81

Mutation Taster

=30/70

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over