rs779958981

Variant names:

• chrX-70927840-C-A
• rs779958981
• NM_032803.6:c.1001G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-70927840-C-A
• chrX-70927840-C-T

Variant summary

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

The NM_032803.6(SLC7A3):​c.1001G>T​(p.Arg334Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000928 in 1,077,703 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R334H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 1 hem.)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 1 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

ENSG00000295939 (HGNC:):

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.1001G>T	p.Arg334Leu	missense	Exon 6 of 12	NP_116192.4
	SLC7A3	NM_001048164.3		c.1001G>T	p.Arg334Leu	missense	Exon 6 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.1001G>T	p.Arg334Leu	missense	Exon 6 of 12	ENSP00000363417.3	Q8WY07
	SLC7A3	ENST00000921007.1		c.1001G>T	p.Arg334Leu	missense	Exon 6 of 13	ENSP00000591066.1
	SLC7A3	ENST00000921008.1		c.1001G>T	p.Arg334Leu	missense	Exon 6 of 13	ENSP00000591067.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000686 AC: 1 AN: 145730 AF XY: 0.0000223

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000148

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.28e-7 AC: 1 AN: 1077703 Hom.: 0 Cov.: 32 AF XY: 0.00000285 AC XY: 1 AN XY: 351087

African (AFR) AF: 0.00 AC: 0 AN: 26011

American (AMR) AF: 0.00 AC: 0 AN: 31388

Ashkenazi Jewish (ASJ) AF: 0.0000528 AC: 1 AN: 18934

East Asian (EAS) AF: 0.00 AC: 0 AN: 29296

South Asian (SAS) AF: 0.00 AC: 0 AN: 51493

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4113

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831731

Other (OTH) AF: 0.00 AC: 0 AN: 45465

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.0
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.021	D
Sift4G	Benign	0.12	T
Polyphen		0.14	B
Vest4		0.61
MutPred		0.64		Loss of methylation at R334 (P = 0.0075)
MVP		0.90
MPC		0.97
ClinPred		0.97	D
GERP RS		3.3
Varity_R		0.82
gMVP		0.86
Mutation Taster		=91/9	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: rs779958981; hg19: chrX-70147690;