chrX-70927864-A-C

Position:

• chrX-70927864-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032803.6(SLC7A3):​c.977T>G​(p.Leu326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,087,557 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000028 (0 hom. 3 hem.)
• Consequence: SLC7A3 NM_032803.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18537918).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A3	NM_032803.6	c.977T>G	p.Leu326Arg	missense_variant	6/12	ENST00000374299.8	NP_116192.4
SLC7A3	NM_001048164.3	c.977T>G	p.Leu326Arg	missense_variant	6/12		NP_001041629.1
SLC7A3	XM_047442598.1	c.977T>G	p.Leu326Arg	missense_variant	5/11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8	c.977T>G	p.Leu326Arg	missense_variant	6/12	1	NM_032803.6	ENSP00000363417.3
SLC7A3	ENST00000298085.4	c.977T>G	p.Leu326Arg	missense_variant	6/12	2		ENSP00000298085.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000276 AC: 3 AN: 1087557 Hom.: 0 Cov.: 32 AF XY: 0.00000843 AC XY: 3 AN XY: 355723

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000239

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2023

The c.977T>G (p.L326R) alteration is located in exon 6 (coding exon 5) of the SLC7A3 gene. This alteration results from a T to G substitution at nucleotide position 977, causing the leucine (L) at amino acid position 326 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.0027	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T;T
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.51	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0050	B;B
Vest4		0.43
MutPred		0.36		Loss of stability (P = 0.0459);Loss of stability (P = 0.0459);
MVP		0.66
MPC		1.2
ClinPred		0.14	T
GERP RS		1.1
Varity_R		0.32
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70147714;