chrX-70925823-T-C

Variant names:

• chrX-70925823-T-C
• rs1447181189
• NM_032803.6:c.1850A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032803.6(SLC7A3):​c.1850A>G​(p.His617Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,209,271 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.693
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16077954).

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.1850A>G	p.His617Arg	missense	Exon 12 of 12	NP_116192.4
	SLC7A3	NM_001048164.3		c.1850A>G	p.His617Arg	missense	Exon 12 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.1850A>G	p.His617Arg	missense	Exon 12 of 12	ENSP00000363417.3	Q8WY07
	SLC7A3	ENST00000921007.1		c.1901A>G	p.His634Arg	missense	Exon 13 of 13	ENSP00000591066.1
	SLC7A3	ENST00000921008.1		c.1901A>G	p.His634Arg	missense	Exon 13 of 13	ENSP00000591067.1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111221 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098050 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363424

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.0000284 AC: 1 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4067

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842052

Other (OTH) AF: 0.00 AC: 0 AN: 46083

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111221 Hom.: 0 Cov.: 22 AF XY: 0.0000299 AC XY: 1 AN XY: 33417

African (AFR) AF: 0.00 AC: 0 AN: 30540

American (AMR) AF: 0.000192 AC: 2 AN: 10390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3546

South Asian (SAS) AF: 0.00 AC: 0 AN: 2624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5985

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53092

Other (OTH) AF: 0.00 AC: 0 AN: 1485

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.062
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.2
DANN	Benign	0.96
DEOGEN2	Benign	0.040	T
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.69
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.13
Sift	Benign	0.071	T
Sift4G	Benign	0.29	T
Polyphen		0.31	B
Vest4		0.24
MutPred		0.36		Gain of MoRF binding (P = 0.0526)
MVP		0.77
MPC		0.57
ClinPred		0.085	T
GERP RS		1.5
Varity_R		0.062
gMVP		0.45
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: rs1447181189; hg19: chrX-70145673;