Genetic Variant SLC7A5:p.Val382Met (chr16-87836644-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003486.7(SLC7A5):c.1144G>A(p.Val382Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V382L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC7A5
NM_003486.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.70

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:

ENSG00000260466 (HGNC:58301):

ENSG00000260466 links:

LOC124903753 (HGNC:):

LOC124903753 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24688327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A5	NM_003486.7 link	c.1144G>A	p.Val382Met	missense_variant	Exon 8 of 10	ENST00000261622.5	NP_003477.4	Q01650
LOC124903753	XR_007065175.1 link	n.380C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC7A5	ENST00000261622.5 link	c.1144G>A	p.Val382Met	missense_variant	Exon 8 of 10	1	NM_003486.7	ENSP00000261622.4	Q01650
SLC7A5	ENST00000565644.5 link	c.346G>A	p.Val116Met	missense_variant	Exon 8 of 10	1		ENSP00000454323.1	A0A0C4DGL4
SLC7A5	ENST00000563489.1 link	n.162G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
ENSG00000260466	ENST00000563687.1 link	n.113C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460076

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726360

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.053

DANN

Benign

0.94

DEOGEN2

Benign

0.021

T;D

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.74

T;T

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.25

T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

0.98

.;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.44

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.13

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.68

.;P

Vest4

0.36

MutPred

0.61

.;Loss of glycosylation at T380 (P = 0.3288);

MVP

0.54

MPC

1.2

ClinPred

0.18

GERP RS

-9.2

Varity_R

0.12

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over