17-19555659-C-T

Position:

• chr17-19555659-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000270570.8(SLC47A1):​c.708C>T​(p.Leu236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,614,214 control chromosomes in the GnomAD database, including 383 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 0.0089 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (327 hom.)
• Consequence: SLC47A1 ENST00000270570.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC47A1	NM_018242.3	c.708C>T	p.Leu236=	synonymous_variant	8/17	ENST00000270570.8	NP_060712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC47A1	ENST00000270570.8	c.708C>T	p.Leu236=	synonymous_variant	8/17	1	NM_018242.3	ENSP00000270570	P1

Frequencies

GnomAD3 genomes AF: 0.00882 AC: 1343 AN: 152204 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0180 AC: 4533 AN: 251478 Hom.: 193 AF XY: 0.0143 AC XY: 1944 AN XY: 135916

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.0909

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0652

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.00536 AC: 7834 AN: 1461892 Hom.: 327 Cov.: 32 AF XY: 0.00483 AC XY: 3509 AN XY: 727246

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0790

Gnomad4 SAS exome AF: 0.00152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.00702

GnomAD4 genome AF: 0.00887 AC: 1351 AN: 152322 Hom.: 56 Cov.: 32 AF XY: 0.00992 AC XY: 739 AN XY: 74478

Gnomad4 AFR AF: 0.00286

Gnomad4 AMR AF: 0.0542

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0670

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00708 Hom.: 23

Bravo AF: 0.0131

Asia WGS AF: 0.0340 AC: 119 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.0
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs16960203; hg19: chr17-19458972;