rs151261004

Variant names:

• chr14-22778843-T-G
• rs151261004
• NM_003982.4:c.720A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_003982.4(SLC7A7):​c.720A>C​(p.Ser240Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 1,614,198 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: SLC7A7 NM_003982.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:8
• Conservation: PhyloP100: -6.39
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 14-22778843-T-G is Benign according to our data. Variant chr14-22778843-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 312821.
• BP7: Synonymous conserved (PhyloP=-6.39 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00257 (391/152324) while in subpopulation AFR AF = 0.00849 (353/41566). AF 95% confidence interval is 0.00776. There are 0 homozygotes in GnomAd4. There are 179 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003982.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	NM_003982.4	MANE Select	c.720A>C	p.Ser240Ser	synonymous	Exon 4 of 10	NP_003973.3
	SLC7A7	NM_001126105.3		c.720A>C	p.Ser240Ser	synonymous	Exon 5 of 11	NP_001119577.1
	SLC7A7	NM_001126106.4		c.720A>C	p.Ser240Ser	synonymous	Exon 5 of 11	NP_001119578.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000674313.1	MANE Select	c.720A>C	p.Ser240Ser	synonymous	Exon 4 of 10	ENSP00000501493.1
	SLC7A7	ENST00000397528.8	TSL:1	c.720A>C	p.Ser240Ser	synonymous	Exon 5 of 11	ENSP00000380662.4
	SLC7A7	ENST00000397529.6	TSL:1	c.720A>C	p.Ser240Ser	synonymous	Exon 4 of 10	ENSP00000380663.2

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 388 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000704 AC: 177 AN: 251456 AF XY: 0.000456

Gnomad AFR exome AF: 0.00874

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000285 AC: 416 AN: 1461874 Hom.: 2 Cov.: 31 AF XY: 0.000237 AC XY: 172 AN XY: 727242

African (AFR) AF: 0.00881 AC: 295 AN: 33480

American (AMR) AF: 0.000917 AC: 41 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1112002

Other (OTH) AF: 0.000762 AC: 46 AN: 60394

GnomAD4 genome AF: 0.00257 AC: 391 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74496

African (AFR) AF: 0.00849 AC: 353 AN: 41566

American (AMR) AF: 0.00176 AC: 27 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00113 Hom.: 2

Bravo AF: 0.00322

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	4	Lysinuric protein intolerance (4)
-	-	4	not provided (4)
-	1	-	Autoinflammatory syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		-6.4
Mutation Taster		=286/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs151261004; hg19: chr14-23248052;