chr8-86217510-C-T

Variant names:

• chr8-86217510-C-T
• rs4419794
• NM_138817.3:c.1139G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138817.3(SLC7A13):​c.1139G>A​(p.Arg380Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,597,544 control chromosomes in the GnomAD database, including 20,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1783 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19063 hom.)
• Consequence: SLC7A13 NM_138817.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16
• Publications: 21 publications found

Genes affected

SLC7A13 (HGNC:23092): (solute carrier family 7 member 13) Predicted to enable L-amino acid transmembrane transporter activity. Predicted to be involved in L-cystine transport; L-glutamate transmembrane transport; and aspartate transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062551796).
• BP6: Variant 8-86217510-C-T is Benign according to our data. Variant chr8-86217510-C-T is described in ClinVar as Benign. ClinVar VariationId is 1600690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138817.3. 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
	SLC7A13	NM_138817.3	MANE Select	c.1139G>A	p.Arg380Lys	missense	Exon 3 of 4	NP_620172.2	Q8TCU3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A13	ENST00000297524.8	TSL:1 MANE Select	c.1139G>A	p.Arg380Lys	missense	Exon 3 of 4	ENSP00000297524.3	Q8TCU3-1
	SLC7A13	ENST00000419776.2	TSL:1	c.1112G>A	p.Arg371Lys	missense	Exon 3 of 5	ENSP00000410982.2	Q8TCU3-2
	SLC7A13	ENST00000520624.1	TSL:4	n.*116G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19709 AN: 151928 Hom.: 1778 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.181 AC: 42933 AN: 237322 AF XY: 0.186

Gnomad AFR exome AF: 0.0559

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.330

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.148 AC: 213757 AN: 1445498 Hom.: 19063 Cov.: 31 AF XY: 0.154 AC XY: 110429 AN XY: 718832

African (AFR) AF: 0.0507 AC: 1650 AN: 32566

American (AMR) AF: 0.228 AC: 9445 AN: 41450

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4819 AN: 25180

East Asian (EAS) AF: 0.324 AC: 12792 AN: 39522

South Asian (SAS) AF: 0.318 AC: 26500 AN: 83324

European-Finnish (FIN) AF: 0.118 AC: 6234 AN: 52938

Middle Eastern (MID) AF: 0.265 AC: 1424 AN: 5370

European-Non Finnish (NFE) AF: 0.128 AC: 141412 AN: 1105498

Other (OTH) AF: 0.159 AC: 9481 AN: 59650

GnomAD4 genome AF: 0.130 AC: 19725 AN: 152046 Hom.: 1783 Cov.: 32 AF XY: 0.134 AC XY: 9931 AN XY: 74324

African (AFR) AF: 0.0558 AC: 2315 AN: 41512

American (AMR) AF: 0.177 AC: 2701 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3466

East Asian (EAS) AF: 0.333 AC: 1722 AN: 5168

South Asian (SAS) AF: 0.322 AC: 1551 AN: 4814

European-Finnish (FIN) AF: 0.115 AC: 1212 AN: 10568

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9032 AN: 67954

Other (OTH) AF: 0.151 AC: 317 AN: 2106

Alfa AF: 0.141 Hom.: 5846

Bravo AF: 0.128

TwinsUK AF: 0.130 AC: 483

ALSPAC AF: 0.120 AC: 461

ESP6500AA AF: 0.0565 AC: 248

ESP6500EA AF: 0.127 AC: 1088

ExAC AF: 0.179 AC: 21712

Asia WGS AF: 0.327 AC: 1134 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.73
DANN	Benign	0.36
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.038
MPC		0.0083
ClinPred		0.0014	T
GERP RS		-0.76
Varity_R		0.041
gMVP		0.30
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4419794; hg19: chr8-87229739; COSMIC: COSV52534112; COSMIC: COSV52534112;