chrX-70925823-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032803.6(SLC7A3):​c.1850A>C​(p.His617Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 111,221 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. 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. H617R) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14168578).

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>C	p.His617Pro	missense	Exon 12 of 12	NP_116192.4
	SLC7A3	NM_001048164.3		c.1850A>C	p.His617Pro	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>C	p.His617Pro	missense	Exon 12 of 12	ENSP00000363417.3	Q8WY07
	SLC7A3	ENST00000921007.1		c.1901A>C	p.His634Pro	missense	Exon 13 of 13	ENSP00000591066.1
	SLC7A3	ENST00000921008.1		c.1901A>C	p.His634Pro	missense	Exon 13 of 13	ENSP00000591067.1

Frequencies

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

Gnomad AFR AF: 0.0000655

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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 Cov.: 30

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: 0.0000655 AC: 2 AN: 30540

American (AMR) AF: 0.00 AC: 0 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.031	T
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.69
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.16
Sift	Uncertain	0.014	D
Sift4G	Benign	0.079	T
Polyphen		0.0010	B
Vest4		0.31
MutPred		0.29		Loss of sheet (P = 0.0315)
MVP		0.65
MPC		0.79
ClinPred		0.088	T
GERP RS		1.5
Varity_R		0.13
gMVP		0.45
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;