rs77474263

chr17-19548051-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018242.3(SLC47A1):c.373C>T(p.Leu125Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,614,144 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0082 (59 hom., cov: 31)
  • Exomes 𝑓: 0.0049 (464 hom.)
• Consequence: SLC47A1 NM_018242.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

Genes affected

SLC47A1 (HGNC:25588): (solute carrier family 47 member 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It encodes a protein of unknown function. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039165616).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC47A1	NM_018242.3	c.373C>T	p.Leu125Phe	missense_variant	4/17	ENST00000270570.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC47A1	ENST00000270570.8	c.373C>T	p.Leu125Phe	missense_variant	4/17	1	NM_018242.3	P1

Frequencies

GnomAD3 genomes AF: 0.00818 AC: 1245 AN: 152194 Hom.: 58 Cov.: 31

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.0209 AC: 5259 AN: 251360 Hom.: 389 AF XY: 0.0157 AC XY: 2136 AN XY: 135874

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00516

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.00486

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.0143

GnomAD4 exome AF: 0.00487 AC: 7119 AN: 1461832 Hom.: 464 Cov.: 30 AF XY: 0.00417 AC XY: 3030 AN XY: 727224

Gnomad4 AFR exome AF: 0.000836

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.0109

Gnomad4 EAS exome AF: 0.00731

Gnomad4 SAS exome AF: 0.000742

Gnomad4 FIN exome AF: 0.00480

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.00820 AC: 1249 AN: 152312 Hom.: 59 Cov.: 31 AF XY: 0.00990 AC XY: 737 AN XY: 74462

Gnomad4 AFR AF: 0.000745

Gnomad4 AMR AF: 0.0698

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00259 Hom.: 4

Bravo AF: 0.0132

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.0157 AC: 1901

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.090
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.049	T;T;.;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;D;D
MetaRNN	Benign	0.0039	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.9	D;D;.;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0030	D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.39
MPC		0.72
ClinPred		0.022	T
GERP RS		4.0
Varity_R		0.57
gMVP		0.42

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: rs77474263; hg19: chr17-19451364; COSMIC: COSV54503654;