rs1061040

Variant names:

• chr14-22773619-T-A
• rs1061040
• NM_003982.4:c.1527A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-22773619-T-A
• chr14-22773619-T-C
• chr14-22773619-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003982.4(SLC7A7):​c.1527A>T​(p.Lys509Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Synonymous variant affecting the same amino acid position (i.e. K509K) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC7A7 NM_003982.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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]

ACMG classification

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=0.2004956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A7	NM_003982.4	c.1527A>T	p.Lys509Asn	missense_variant	Exon 10 of 10	ENST00000674313.1	NP_003973.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1	c.1527A>T	p.Lys509Asn	missense_variant	Exon 10 of 10		NM_003982.4	ENSP00000501493.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461544 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 727074

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.0067	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;T;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.68	.;.;.;.;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Uncertain	-0.083	T
MutationAssessor	Benign	1.7	L;L;L;L;L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.40	N;N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.10	T;T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T;D
Polyphen		1.0	D;D;D;D;D;.
Vest4		0.41
MutPred		0.16		Loss of ubiquitination at K509 (P = 0.0141);Loss of ubiquitination at K509 (P = 0.0141);Loss of ubiquitination at K509 (P = 0.0141);Loss of ubiquitination at K509 (P = 0.0141);Loss of ubiquitination at K509 (P = 0.0141);.;
MVP		0.59
MPC		0.23
ClinPred		0.40	T
GERP RS		-0.031
Varity_R		0.065
gMVP		0.55

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

Other links and lift over

dbSNP: rs1061040; hg19: chr14-23242828;