Variant 16-87836548-C-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.1240G>A(p.Gly414Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,368 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SLC7A5
NM_003486.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

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:

(HGNC:):

links:

Genome browser will be placed here

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, 0.884

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A5	NM_003486.7 linkuse as main transcript	c.1240G>A	p.Gly414Ser	missense_variant	8/10	ENST00000261622.5
LOC124903753	XR_007065175.1 linkuse as main transcript	n.284C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC7A5	ENST00000261622.5 linkuse as main transcript	c.1240G>A	p.Gly414Ser	missense_variant	8/10	1	NM_003486.7	P1
SLC7A5	ENST00000565644.5 linkuse as main transcript	c.442G>A	p.Gly148Ser	missense_variant	8/10	1
	ENST00000563687.1 linkuse as main transcript	n.17C>T		non_coding_transcript_exon_variant	1/2	3
SLC7A5	ENST00000563489.1 linkuse as main transcript	n.258G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249952

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461140

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

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 16, 2021

The c.1240G>A (p.G414S) alteration is located in exon 8 (coding exon 8) of the SLC7A5 gene. This alteration results from a G to A substitution at nucleotide position 1240, causing the glycine (G) at amino acid position 414 to be replaced by a serine (S). 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

0.74

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

T;D

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.88

D;D

MetaSVM

Uncertain

0.76

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.7

D;D

Sift

Uncertain

0.024

D;D

Sift4G

Uncertain

0.041

D;D

Polyphen

1.0

.;D

Vest4

0.93

MutPred

0.69

.;Gain of catalytic residue at G414 (P = 0.0632);

MVP

0.97

MPC

1.8

ClinPred

0.78

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.74

gMVP

0.90

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