chr3-170467161-G-A

Position:

• chr3-170467161-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020949.3(SLC7A14):​c.2210C>T​(p.Ala737Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00863 in 1,614,142 control chromosomes in the GnomAD database, including 1,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A737A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.047 (519 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (509 hom.)
• Consequence: SLC7A14 NM_020949.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.98

Genes affected

SLC7A14 (HGNC:29326): (solute carrier family 7 member 14) This gene is predicted to encode a glycosylated, cationic amino acid transporter protein with 14 transmembrane domains. This gene is primarily expressed in skin fibroblasts, neural tissue, and primary endothelial cells and its protein is predicted to mediate lysosomal uptake of cationic amino acids. Mutations in this gene are associated with autosomal recessive retinitis pigmentosa. In mice, this gene is expressed in the photoreceptor layer of the retina where its expression increases over the course of retinal development and persists in the mature retina. [provided by RefSeq, Apr 2014]

SLC7A14-AS1 (HGNC:54092): (SLC7A14 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00145486).
• BP6: Variant 3-170467161-G-A is Benign according to our data. Variant chr3-170467161-G-A is described in ClinVar as [Benign]. Clinvar id is 1164372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A14	NM_020949.3	c.2210C>T	p.Ala737Val	missense_variant	8/8	ENST00000231706.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A14	ENST00000231706.6	c.2210C>T	p.Ala737Val	missense_variant	8/8	2	NM_020949.3	P1
SLC7A14-AS1	ENST00000643719.1	n.273+6749G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7112 AN: 152136 Hom.: 519 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0311

GnomAD3 exomes AF: 0.0120 AC: 3025 AN: 251332 Hom.: 226 AF XY: 0.00847 AC XY: 1151 AN XY: 135826

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.00760

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00465 AC: 6805 AN: 1461888 Hom.: 509 Cov.: 31 AF XY: 0.00391 AC XY: 2841 AN XY: 727244

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.00825

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000126

Gnomad4 OTH exome AF: 0.00949

GnomAD4 genome AF: 0.0468 AC: 7122 AN: 152254 Hom.: 519 Cov.: 32 AF XY: 0.0454 AC XY: 3377 AN XY: 74438

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.00962 Hom.: 162

Bravo AF: 0.0526

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.163 AC: 720

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0151 AC: 1833

Asia WGS AF: 0.0100 AC: 37 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.0000035	P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.20
Sift	Benign	0.24	T
Sift4G	Benign	0.44	T
Polyphen		0.20	B
Vest4		0.030
MPC		0.14
ClinPred		0.0038	T
GERP RS		3.1
Varity_R		0.036
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs73040363; hg19: chr3-170184949;