rs190717111

Variant names:

• chr8-42417394-T-C
• rs190717111
• NM_001257180.2:c.*409A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-42417394-T-C
• chr8-42417394-T-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001257180.2(SLC20A2):​c.*409A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00048 in 158,390 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: SLC20A2 NM_001257180.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

SLC20A2 (HGNC:10947): (solute carrier family 20 member 2) This gene encodes a member of the inorganic phosphate transporter family. The encoded protein is a type 3 sodium-dependent phosphate symporter that plays an important role in phosphate homeostasis by mediating cellular phosphate uptake. The encoded protein also confers susceptibility to viral infection as a gamma-retroviral receptor. Mutations in this gene may play a role in familial idiopathic basal ganglia calcification. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

SLC20A2 Gene-Disease associations (from GenCC):

• basal ganglia calcification, idiopathic, 1

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000486 (74/152308) while in subpopulation NFE AF = 0.00047 (32/68024). AF 95% confidence interval is 0.000342. There are 1 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 74 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257180.2. 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
	SLC20A2	NM_001257180.2	MANE Select	c.*409A>G		3_prime_UTR	Exon 11 of 11	NP_001244109.1	A0A384MR38
	SLC20A2	NM_001257181.2		c.*409A>G		3_prime_UTR	Exon 11 of 11	NP_001244110.1	Q08357
	SLC20A2	NM_006749.5		c.*409A>G		3_prime_UTR	Exon 11 of 11	NP_006740.1	Q08357

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC20A2	ENST00000520262.6	TSL:2 MANE Select	c.*409A>G		3_prime_UTR	Exon 11 of 11	ENSP00000429754.1	Q08357
	SLC20A2	ENST00000342228.7	TSL:1	c.*409A>G		3_prime_UTR	Exon 11 of 11	ENSP00000340465.3	Q08357
	SLC20A2	ENST00000965915.1		c.*409A>G		3_prime_UTR	Exon 12 of 12	ENSP00000635974.1

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152190 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000329 AC: 2 AN: 6082 Hom.: 0 Cov.: 0 AF XY: 0.000623 AC XY: 2 AN XY: 3210

African (AFR) AF: 0.00 AC: 0 AN: 248

American (AMR) AF: 0.00 AC: 0 AN: 1358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 144

East Asian (EAS) AF: 0.00 AC: 0 AN: 492

South Asian (SAS) AF: 0.00 AC: 0 AN: 650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.000685 AC: 2 AN: 2920

Other (OTH) AF: 0.00 AC: 0 AN: 216

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152308 Hom.: 1 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74486

African (AFR) AF: 0.000144 AC: 6 AN: 41570

American (AMR) AF: 0.000196 AC: 3 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.000484

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Idiopathic basal ganglia calcification 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		2.3
Mutation Taster		=100/0	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: rs190717111; hg19: chr8-42274912;