rs1805061

Variant names:

• chr14-22778903-A-G
• rs1805061
• NM_003982.4:c.660T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003982.4(SLC7A7):​c.660T>C​(p.Gly220Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,810 control chromosomes in the GnomAD database, including 20,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2989 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17813 hom.)
• Consequence: SLC7A7 NM_003982.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9 O:1
• Conservation: PhyloP100: -0.623
• Publications: 23 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 14-22778903-A-G is Benign according to our data. Variant chr14-22778903-A-G is described in ClinVar as Benign. ClinVar VariationId is 139196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.623 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	NM_003982.4	MANE Select	c.660T>C	p.Gly220Gly	synonymous	Exon 4 of 10	NP_003973.3
	SLC7A7	NM_001126105.3		c.660T>C	p.Gly220Gly	synonymous	Exon 5 of 11	NP_001119577.1
	SLC7A7	NM_001126106.4		c.660T>C	p.Gly220Gly	synonymous	Exon 5 of 11	NP_001119578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000674313.1	MANE Select	c.660T>C	p.Gly220Gly	synonymous	Exon 4 of 10	ENSP00000501493.1
	SLC7A7	ENST00000397528.8	TSL:1	c.660T>C	p.Gly220Gly	synonymous	Exon 5 of 11	ENSP00000380662.4
	SLC7A7	ENST00000397529.6	TSL:1	c.660T>C	p.Gly220Gly	synonymous	Exon 4 of 10	ENSP00000380663.2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28155 AN: 151982 Hom.: 2975 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.186 AC: 46620 AN: 251284 AF XY: 0.173

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.0928

Gnomad EAS exome AF: 0.351

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.146 AC: 213548 AN: 1461710 Hom.: 17813 Cov.: 32 AF XY: 0.144 AC XY: 104497 AN XY: 727160

African (AFR) AF: 0.251 AC: 8407 AN: 33478

American (AMR) AF: 0.342 AC: 15303 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0941 AC: 2459 AN: 26134

East Asian (EAS) AF: 0.318 AC: 12623 AN: 39692

South Asian (SAS) AF: 0.117 AC: 10121 AN: 86242

European-Finnish (FIN) AF: 0.146 AC: 7824 AN: 53418

Middle Eastern (MID) AF: 0.0972 AC: 559 AN: 5750

European-Non Finnish (NFE) AF: 0.132 AC: 147309 AN: 1111910

Other (OTH) AF: 0.148 AC: 8943 AN: 60380

GnomAD4 genome AF: 0.185 AC: 28197 AN: 152100 Hom.: 2989 Cov.: 32 AF XY: 0.186 AC XY: 13852 AN XY: 74360

African (AFR) AF: 0.254 AC: 10535 AN: 41478

American (AMR) AF: 0.257 AC: 3931 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 346 AN: 3472

East Asian (EAS) AF: 0.341 AC: 1758 AN: 5156

South Asian (SAS) AF: 0.120 AC: 579 AN: 4818

European-Finnish (FIN) AF: 0.149 AC: 1578 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8941 AN: 68006

Other (OTH) AF: 0.182 AC: 384 AN: 2108

Alfa AF: 0.146 Hom.: 4419

Bravo AF: 0.198

Asia WGS AF: 0.236 AC: 818 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.128

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Lysinuric protein intolerance (4)
-	-	4	not specified (4)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.5
DANN	Benign	0.72
PhyloP100		-0.62
Mutation Taster		=296/4	polymorphism (auto)

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: rs1805061; hg19: chr14-23248112; COSMIC: COSV53541629; COSMIC: COSV53541629;