17-19534026-C-T

Variant names:

• chr17-19534026-C-T
• rs61733934
• NM_018242.3:c.87C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_018242.3(SLC47A1):​c.87C>T​(p.Ser29Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,547,452 control chromosomes in the GnomAD database, including 172 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 0.0096 (11 hom., cov: 32)
  • Exomes 𝑓: 0.013 (161 hom.)
• Consequence: SLC47A1 NM_018242.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00964 (1469/152328) while in subpopulation SAS AF = 0.0234 (113/4832). AF 95% confidence interval is 0.0199. There are 11 homozygotes in GnomAd4. There are 709 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018242.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	NM_018242.3	MANE Select	c.87C>T	p.Ser29Ser	synonymous	Exon 1 of 17	NP_060712.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	ENST00000270570.8	TSL:1 MANE Select	c.87C>T	p.Ser29Ser	synonymous	Exon 1 of 17	ENSP00000270570.4
	SLC47A1	ENST00000395585.5	TSL:1	c.87C>T	p.Ser29Ser	synonymous	Exon 1 of 19	ENSP00000378951.1
	SLC47A1	ENST00000575023.5	TSL:1	c.87C>T	p.Ser29Ser	synonymous	Exon 1 of 7	ENSP00000460164.1

Frequencies

GnomAD3 genomes AF: 0.00966 AC: 1470 AN: 152212 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.0131 AC: 1924 AN: 146932 AF XY: 0.0148

Gnomad AFR exome AF: 0.00192

Gnomad AMR exome AF: 0.00767

Gnomad ASJ exome AF: 0.0262

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00412

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0155

GnomAD4 exome AF: 0.0125 AC: 17472 AN: 1395124 Hom.: 161 Cov.: 32 AF XY: 0.0133 AC XY: 9149 AN XY: 688936

African (AFR) AF: 0.00264 AC: 81 AN: 30694

American (AMR) AF: 0.00872 AC: 312 AN: 35792

Ashkenazi Jewish (ASJ) AF: 0.0244 AC: 608 AN: 24950

East Asian (EAS) AF: 0.000112 AC: 4 AN: 35574

South Asian (SAS) AF: 0.0257 AC: 2001 AN: 77996

European-Finnish (FIN) AF: 0.00476 AC: 228 AN: 47876

Middle Eastern (MID) AF: 0.0274 AC: 134 AN: 4896

European-Non Finnish (NFE) AF: 0.0124 AC: 13357 AN: 1079492

Other (OTH) AF: 0.0129 AC: 747 AN: 57854

GnomAD4 genome AF: 0.00964 AC: 1469 AN: 152328 Hom.: 11 Cov.: 32 AF XY: 0.00952 AC XY: 709 AN XY: 74496

African (AFR) AF: 0.00255 AC: 106 AN: 41594

American (AMR) AF: 0.0112 AC: 172 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4832

European-Finnish (FIN) AF: 0.00518 AC: 55 AN: 10628

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0125 AC: 852 AN: 68008

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.0128 Hom.: 12

Bravo AF: 0.00984

Asia WGS AF: 0.00867 AC: 30 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.9
DANN	Benign	0.92
PhyloP100		-1.2
PromoterAI		0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61733934; hg19: chr17-19437339;