rs200077616

Variant names:

• chr8-17538911-C-A
• rs200077616
• ENST00000004531.14:c.87C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-17538911-C-A
• chr8-17538911-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001164771.2(SLC7A2):​c.87C>A​(p.Ser29Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,612,652 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: SLC7A2 NM_001164771.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.666
• Publications: 5 publications found

Genes affected

SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04476419).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164771.2. 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
	SLC7A2	NM_001370338.1	MANE Select	c.-22-4407C>A		intron	N/A	NP_001357267.1	P52569-1
	SLC7A2	NM_001164771.2		c.87C>A	p.Ser29Arg	missense	Exon 1 of 12	NP_001158243.1	P52569-3
	SLC7A2	NM_003046.6		c.87C>A	p.Ser29Arg	missense	Exon 1 of 12	NP_003037.4	P52569-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A2	ENST00000004531.14	TSL:1	c.87C>A	p.Ser29Arg	missense	Exon 1 of 12	ENSP00000004531.10	P52569-3
	SLC7A2	ENST00000398090.3	TSL:1	c.87C>A	p.Ser29Arg	missense	Exon 1 of 12	ENSP00000381164.3	P52569-2
	SLC7A2	ENST00000640220.1	TSL:1	c.-34C>A		5_prime_UTR	Exon 1 of 12	ENSP00000492016.2	P52569-1

Frequencies

GnomAD3 genomes AF: 0.000803 AC: 122 AN: 151940 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000581 AC: 145 AN: 249362 AF XY: 0.000621

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00110

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00140 AC: 2048 AN: 1460594 Hom.: 2 Cov.: 30 AF XY: 0.00137 AC XY: 995 AN XY: 726664

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000896 AC: 3 AN: 33464

American (AMR) AF: 0.000179 AC: 8 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86236

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00174 AC: 1938 AN: 1110802

Other (OTH) AF: 0.000845 AC: 51 AN: 60378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000802 AC: 122 AN: 152058 Hom.: 0 Cov.: 33 AF XY: 0.000700 AC XY: 52 AN XY: 74326

African (AFR) AF: 0.000338 AC: 14 AN: 41444

American (AMR) AF: 0.000131 AC: 2 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5142

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00151 AC: 103 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000967 Hom.: 1

Bravo AF: 0.000729

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00159 AC: 13

ExAC AF: 0.000530 AC: 64

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.59
DANN	Benign	0.97
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.20	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.35	T
PhyloP100		-0.67
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.20
Sift	Benign	0.075	T
Sift4G	Uncertain	0.034	D
Polyphen		0.73	P
Vest4		0.17
MutPred		0.32		Gain of sheet (P = 0.0101)
MVP		0.69
MPC		0.021
ClinPred		0.030	T
GERP RS		1.9
PromoterAI		-0.043	Neutral
gMVP		0.21
Mutation Taster		=98/2	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: rs200077616; hg19: chr8-17396420;