chr8-86214418-C-A

Variant names:

• chr8-86214418-C-A
• rs9693999
• NM_138817.3:c.1408G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138817.3(SLC7A13):​c.1408G>T​(p.Glu470*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC7A13 NM_138817.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A13	NM_138817.3	MANE Select	c.1408G>T	p.Glu470*	stop_gained	Exon 4 of 4	NP_620172.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A13	ENST00000297524.8	TSL:1 MANE Select	c.1408G>T	p.Glu470*	stop_gained	Exon 4 of 4	ENSP00000297524.3
	SLC7A13	ENST00000419776.2	TSL:1	c.*207G>T		3_prime_UTR	Exon 5 of 5	ENSP00000410982.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444418 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 719322

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

African (AFR) AF: 0.00 AC: 0 AN: 32932

American (AMR) AF: 0.00 AC: 0 AN: 43870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39422

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101910

Other (OTH) AF: 0.00 AC: 0 AN: 59804

⚠️ 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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Benign	0.97
Eigen	Uncertain	0.26
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.16	N
PhyloP100		2.7
Vest4		0.070
GERP RS		2.3
Mutation Taster		=97/3	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: rs9693999; hg19: chr8-87226647;