X-70927840-C-T

Variant names:

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

Variant summary

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

The NM_032803.6(SLC7A3):​c.1001G>A​(p.Arg334His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000857 in 1,190,210 control chromosomes in the GnomAD database, including 1 homozygotes. There are 45 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000092 (1 hom. 44 hem.)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.060182065).
• BS2: High AC in GnomAdExome4 at 99 AD gene.

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>A	p.Arg334His	missense	Exon 6 of 12	NP_116192.4
	SLC7A3	NM_001048164.3		c.1001G>A	p.Arg334His	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>A	p.Arg334His	missense	Exon 6 of 12	ENSP00000363417.3	Q8WY07
	SLC7A3	ENST00000921007.1		c.1001G>A	p.Arg334His	missense	Exon 6 of 13	ENSP00000591066.1
	SLC7A3	ENST00000921008.1		c.1001G>A	p.Arg334His	missense	Exon 6 of 13	ENSP00000591067.1

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 AN: 112506 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000936

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000734

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000178 AC: 26 AN: 145730 AF XY: 0.000290

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

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: 0.0000919 AC: 99 AN: 1077704 Hom.: 1 Cov.: 32 AF XY: 0.000125 AC XY: 44 AN XY: 351088

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

American (AMR) AF: 0.000127 AC: 4 AN: 31388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18934

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

South Asian (SAS) AF: 0.00144 AC: 74 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: 0.0000108 AC: 9 AN: 831732

Other (OTH) AF: 0.000264 AC: 12 AN: 45465

GnomAD4 genome AF: 0.0000267 AC: 3 AN: 112506 Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1 AN XY: 34654

African (AFR) AF: 0.00 AC: 0 AN: 30999

American (AMR) AF: 0.0000936 AC: 1 AN: 10679

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.000734 AC: 2 AN: 2726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6135

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53298

Other (OTH) AF: 0.00 AC: 0 AN: 1514

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.000210 AC: 25

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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	20
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.60	D
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.060	T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	1.9	L
PhyloP100		1.0
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.018	D
Sift4G	Benign	0.097	T
Polyphen		0.26	B
Vest4		0.068
MutPred		0.66		Loss of methylation at R334 (P = 0.0075)
MVP		0.83
MPC		0.48
ClinPred		0.14	T
GERP RS		3.3
Varity_R		0.57
gMVP		0.66
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: rs779958981; hg19: chrX-70147690;