rs78700676

Variant names:

• chr17-19577397-G-C
• rs78700676
• NM_018242.3:c.1557G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018242.3(SLC47A1):​c.1557G>C​(p.Gln519His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC47A1 NM_018242.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08792853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC47A1	NM_018242.3	c.1557G>C	p.Gln519His	missense_variant	Exon 17 of 17	ENST00000270570.8	NP_060712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC47A1	ENST00000270570.8	c.1557G>C	p.Gln519His	missense_variant	Exon 17 of 17	1	NM_018242.3	ENSP00000270570.4

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74356

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.5
DANN	Benign	0.94
DEOGEN2	Benign	0.064	.;T;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.088	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	.;M;.;M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	.;N;.;N
REVEL	Benign	0.071
Sift	Benign	0.55	.;T;.;T
Sift4G	Uncertain	0.036	D;T;D;T
Polyphen		0.58, 0.032	.;P;.;B
Vest4		0.37
MutPred		0.13		.;Gain of catalytic residue at M521 (P = 0.1003);.;Gain of catalytic residue at M521 (P = 0.1003);
MVP		0.11
MPC		0.34
ClinPred		0.19	T
GERP RS		2.0
Varity_R		0.063
gMVP		0.28

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: rs78700676; hg19: chr17-19480710;