Variant chr14-22813308-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003982.4(SLC7A7):c.91G>A(p.Val31Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC7A7
NM_003982.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

SLC7A7 (HGNC:11065): (solute carrier family 7 member 7) The protein encoded by this gene is the light subunit of a cationic amino acid transporter. This sodium-independent transporter is formed when the light subunit encoded by this gene dimerizes with the heavy subunit transporter protein SLC3A2. This transporter is found in epithelial cell membranes where it transfers cationic and large neutral amino acids from the cell to the extracellular space. Defects in this gene are a cause of lysinuric protein intolerance (LPI). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

SLC7A7 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=0.12680256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC7A7	NM_003982.4 linkuse as main transcript	c.91G>A	p.Val31Met	missense_variant	2/10	ENST00000674313.1	NP_003973.3
SLC7A7	NM_001126105.3 linkuse as main transcript	c.91G>A	p.Val31Met	missense_variant	3/11		NP_001119577.1
SLC7A7	NM_001126106.4 linkuse as main transcript	c.91G>A	p.Val31Met	missense_variant	3/11		NP_001119578.1
SLC7A7	XM_011537299.2 linkuse as main transcript	c.91G>A	p.Val31Met	missense_variant	2/10		XP_011535601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1 linkuse as main transcript	c.91G>A	p.Val31Met	missense_variant	2/10		NM_003982.4	ENSP00000501493	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250604

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135624

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 SAS 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:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.18

T;T;T;T;T;T;.;T;.;T;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.84

.;.;.;.;T;D;D;D;D;D;D;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

0.20

N;N;N;N;N;.;.;.;.;.;.;.

MutationTaster

Benign

0.73

D;D;D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N;N;N;N;N;D

REVEL

Benign

0.26

Sift

Benign

0.24

T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T;.;.;.;.;.;.;T

Polyphen

0.0020

B;B;B;B;B;.;.;.;.;.;.;.

Vest4

0.11

MutPred

0.32

Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);Loss of methylation at K32 (P = 0.0202);

MVP

0.58

MPC

0.20

ClinPred

0.26

GERP RS

2.5

Varity_R

0.056

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over