14-22813308-C-T

Variant names:

• chr14-22813308-C-T
• rs142956369
• NM_003982.4:c.91G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/22 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. V31L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC7A7 NM_003982.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• lysinuric protein intolerance

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
SLC7A7	NM_003982.4	c.91G>A	p.Val31Met	missense_variant	Exon 2 of 10	ENST00000674313.1	NP_003973.3
SLC7A7	NM_001126105.3	c.91G>A	p.Val31Met	missense_variant	Exon 3 of 11		NP_001119577.1
SLC7A7	NM_001126106.4	c.91G>A	p.Val31Met	missense_variant	Exon 3 of 11		NP_001119578.1
SLC7A7	XM_011537299.2	c.91G>A	p.Val31Met	missense_variant	Exon 2 of 10		XP_011535601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1	c.91G>A	p.Val31Met	missense_variant	Exon 2 of 10		NM_003982.4	ENSP00000501493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250604 AF XY: 0.00000737

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: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

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	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
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	D
LIST_S2	Benign	0.84	.;.;.;.;T;D;D;D;D;D;D;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	0.20	N;N;N;N;N;.;.;.;.;.;.;.
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
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	T
GERP RS		2.5
Varity_R		0.056
gMVP		0.17
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs142956369; hg19: chr14-23282517; COSMIC: COSV99591691; COSMIC: COSV99591691;