rs11568438

Variant names:

• chr14-22813127-G-A
• rs11568438
• NM_003982.4:c.272C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-22813127-G-A
• chr14-22813127-G-T
• chr14-22813127-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003982.4(SLC7A7):​c.272C>T​(p.Ala91Val) variant causes a missense change. The variant allele was found at a frequency of 0.016 in 1,614,104 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A91E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.013 (19 hom., cov: 31)
  • Exomes 𝑓: 0.016 (242 hom.)
• Consequence: SLC7A7 NM_003982.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11 O:1
• Conservation: PhyloP100: 6.88
• Publications: 11 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014431596).
• BP6: Variant 14-22813127-G-A is Benign according to our data. Variant chr14-22813127-G-A is described in ClinVar as Benign. ClinVar VariationId is 380186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0128 (1949/152212) while in subpopulation NFE AF = 0.0211 (1437/68006). AF 95% confidence interval is 0.0202. There are 19 homozygotes in GnomAd4. There are 901 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 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.272C>T	p.Ala91Val	missense	Exon 2 of 10	NP_003973.3
	SLC7A7	NM_001126105.3		c.272C>T	p.Ala91Val	missense	Exon 3 of 11	NP_001119577.1	A0A0S2Z502
	SLC7A7	NM_001126106.4		c.272C>T	p.Ala91Val	missense	Exon 3 of 11	NP_001119578.1	Q9UM01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000674313.1	MANE Select	c.272C>T	p.Ala91Val	missense	Exon 2 of 10	ENSP00000501493.1	Q9UM01
	SLC7A7	ENST00000397528.8	TSL:1	c.272C>T	p.Ala91Val	missense	Exon 3 of 11	ENSP00000380662.4	Q9UM01
	SLC7A7	ENST00000397529.6	TSL:1	c.272C>T	p.Ala91Val	missense	Exon 2 of 10	ENSP00000380663.2	Q9UM01

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1950 AN: 152096 Hom.: 19 Cov.: 31

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00734

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.0125 AC: 3138 AN: 251372 AF XY: 0.0122

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.00512

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0246

Gnomad NFE exome AF: 0.0193

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0163 AC: 23868 AN: 1461892 Hom.: 242 Cov.: 71 AF XY: 0.0160 AC XY: 11618 AN XY: 727246

African (AFR) AF: 0.00239 AC: 80 AN: 33480

American (AMR) AF: 0.00599 AC: 268 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00888 AC: 232 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000614 AC: 53 AN: 86258

European-Finnish (FIN) AF: 0.0247 AC: 1318 AN: 53418

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.0189 AC: 21009 AN: 1112012

Other (OTH) AF: 0.0147 AC: 889 AN: 60396

GnomAD4 genome AF: 0.0128 AC: 1949 AN: 152212 Hom.: 19 Cov.: 31 AF XY: 0.0121 AC XY: 901 AN XY: 74432

African (AFR) AF: 0.00301 AC: 125 AN: 41528

American (AMR) AF: 0.00727 AC: 111 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10604

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0211 AC: 1437 AN: 68006

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.0176 Hom.: 138

Bravo AF: 0.0119

TwinsUK AF: 0.0154 AC: 57

ALSPAC AF: 0.0182 AC: 70

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0201 AC: 173

ExAC AF: 0.0123 AC: 1487

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0184

EpiControl AF: 0.0161

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Lysinuric protein intolerance (4)
-	-	4	not provided (5)
-	-	2	not specified (2)
-	-	1	Autoinflammatory syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.014	T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.15
MPC		0.65
ClinPred		0.011	T
GERP RS		5.4
Varity_R		0.54
gMVP		0.89
Mutation Taster		=37/63	disease causing

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: rs11568438; hg19: chr14-23282336; COSMIC: COSV53539800; COSMIC: COSV53539800;