17-19577330-G-T

Variant names:

• chr17-19577330-G-T
• rs35395280
• NM_018242.3:c.1490G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018242.3(SLC47A1):​c.1490G>T​(p.Cys497Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,613,716 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0088 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (17 hom.)
• Consequence: SLC47A1 NM_018242.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0470
• 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]

ENSG00000262769 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002804488).
• BP6: Variant 17-19577330-G-T is Benign according to our data. Variant chr17-19577330-G-T is described in ClinVar as Benign. ClinVar VariationId is 784669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00885 (1346/152102) while in subpopulation AFR AF = 0.0301 (1247/41492). AF 95% confidence interval is 0.0287. There are 23 homozygotes in GnomAd4. There are 631 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	NM_018242.3	MANE Select	c.1490G>T	p.Cys497Phe	missense	Exon 17 of 17	NP_060712.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	ENST00000270570.8	TSL:1 MANE Select	c.1490G>T	p.Cys497Phe	missense	Exon 17 of 17	ENSP00000270570.4	Q96FL8-1
	SLC47A1	ENST00000395585.5	TSL:1	c.1490G>T	p.Cys497Phe	missense	Exon 17 of 19	ENSP00000378951.1	Q96FL8-3
	SLC47A1	ENST00000571335.5	TSL:1	c.728G>T	p.Cys243Phe	missense	Exon 13 of 13	ENSP00000462630.1	J3KSS8

Frequencies

GnomAD3 genomes AF: 0.00881 AC: 1339 AN: 151984 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00910

GnomAD2 exomes AF: 0.00246 AC: 618 AN: 251150 AF XY: 0.00177

Gnomad AFR exome AF: 0.0322

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000991 AC: 1449 AN: 1461614 Hom.: 17 Cov.: 32 AF XY: 0.000850 AC XY: 618 AN XY: 727082

African (AFR) AF: 0.0310 AC: 1038 AN: 33460

American (AMR) AF: 0.00233 AC: 104 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000127 AC: 141 AN: 1111890

Other (OTH) AF: 0.00217 AC: 131 AN: 60390

GnomAD4 genome AF: 0.00885 AC: 1346 AN: 152102 Hom.: 23 Cov.: 32 AF XY: 0.00849 AC XY: 631 AN XY: 74352

African (AFR) AF: 0.0301 AC: 1247 AN: 41492

American (AMR) AF: 0.00451 AC: 69 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67986

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00747 Hom.: 14

Bravo AF: 0.0109

ESP6500AA AF: 0.0284 AC: 125

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00273 AC: 332

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.72
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.047
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.038
Sift	Benign	0.32	T
Sift4G	Uncertain	0.054	T
Polyphen		0.021	B
Vest4		0.27
MVP		0.11
MPC		0.27
ClinPred		0.0065	T
GERP RS		0.13
Varity_R		0.088
gMVP		0.29
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs35395280; hg19: chr17-19480643; COSMIC: COSV99062013; COSMIC: COSV99062013;