Variant 16-87832995-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003486.7(SLC7A5):c.1499T>A(p.Met500Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC7A5
NM_003486.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

Variant links:

Genes affected

SLC7A5 (HGNC:11063): (solute carrier family 7 member 5) Enables L-leucine transmembrane transporter activity; L-tryptophan transmembrane transporter activity; and thyroid hormone transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Is integral component of membrane. Part of amino acid transport complex; apical plasma membrane; and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A5	NM_003486.7 linkuse as main transcript	c.1499T>A	p.Met500Lys	missense_variant	10/10	ENST00000261622.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC7A5	ENST00000261622.5 linkuse as main transcript	c.1499T>A	p.Met500Lys	missense_variant	10/10	1	NM_003486.7	P1
SLC7A5	ENST00000565644.5 linkuse as main transcript	c.701T>A	p.Met234Lys	missense_variant	10/10	1
SLC7A5	ENST00000563489.1 linkuse as main transcript	n.517T>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.1499T>A (p.M500K) alteration is located in exon 10 (coding exon 10) of the SLC7A5 gene. This alteration results from a T to A substitution at nucleotide position 1499, causing the methionine (M) at amino acid position 500 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.080

T;D

Eigen

Benign

0.018

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Uncertain

0.14

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.6

D;D

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.20

.;B

Vest4

0.58

MutPred

0.81

.;Gain of methylation at M500 (P = 0.0151);

MVP

0.73

MPC

1.4

ClinPred

0.96

GERP RS

5.2

Varity_R

0.89

gMVP

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over