X-70926950-C-T

Variant names:

• chrX-70926950-C-T
• NM_032803.6:c.1378G>A

Variant summary

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

The NM_032803.6(SLC7A3):​c.1378G>A​(p.Gly460Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,819 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.484
• Publications: 0 publications found

Genes affected

SLC7A3 (HGNC:11061): (solute carrier family 7 member 3) This gene encodes a member of the solute carrier family 7. The encoded protein is a sodium-independent cationic amino acid transporter. Alternate splicing results in multiple transcripts that encoded the same protein.[provided by RefSeq, May 2010]

SLC7A3 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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_032803.6. 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
	SLC7A3	NM_032803.6	MANE Select	c.1378G>A	p.Gly460Arg	missense	Exon 9 of 12	NP_116192.4
	SLC7A3	NM_001048164.3		c.1378G>A	p.Gly460Arg	missense	Exon 9 of 12	NP_001041629.1	Q8WY07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A3	ENST00000374299.8	TSL:1 MANE Select	c.1378G>A	p.Gly460Arg	missense	Exon 9 of 12	ENSP00000363417.3	Q8WY07
	SLC7A3	ENST00000921007.1		c.1378G>A	p.Gly460Arg	missense	Exon 9 of 13	ENSP00000591066.1
	SLC7A3	ENST00000921008.1		c.1378G>A	p.Gly460Arg	missense	Exon 9 of 13	ENSP00000591067.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097819 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363177

African (AFR) AF: 0.00 AC: 0 AN: 26388

American (AMR) AF: 0.00 AC: 0 AN: 35165

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841913

Other (OTH) AF: 0.00 AC: 0 AN: 46082

GnomAD4 genome Cov.: 23

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	0.10
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.79
DANN	Benign	0.44
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.48
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.27
Sift	Benign	0.12	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.41
MutPred		0.68		Loss of helix (P = 0.0167)
MVP		0.46
MPC		0.40
ClinPred		0.057	T
GERP RS		2.4
Varity_R		0.063
gMVP		0.61
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

hg19: chrX-70146800;