rs6841

Variant names:

• chr8-42416746-G-C
• rs6841
• NM_001257180.2:c.*1057C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006749.5(SLC20A2):​c.*1057C>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 0.192 in 152,552 control chromosomes in the GnomAD database, including 5,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (5914 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: SLC20A2 NM_006749.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.434
• Publications: 6 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: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-42416746-G-C is Benign according to our data. Variant chr8-42416746-G-C is described in ClinVar as Benign. ClinVar VariationId is 363053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006749.5. 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
	SLC20A2	NM_001257180.2	MANE Select	c.*1057C>G		3_prime_UTR	Exon 11 of 11	NP_001244109.1
	SLC20A2	NM_001257181.2		c.*1057C>G		3_prime_UTR	Exon 11 of 11	NP_001244110.1
	SLC20A2	NM_006749.5		c.*1057C>G		3_prime_UTR	Exon 11 of 11	NP_006740.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC20A2	ENST00000520262.6	TSL:2 MANE Select	c.*1057C>G		3_prime_UTR	Exon 11 of 11	ENSP00000429754.1
	SLC20A2	ENST00000342228.7	TSL:1	c.*1057C>G		3_prime_UTR	Exon 11 of 11	ENSP00000340465.3
	SLC20A2	ENST00000965915.1		c.*1057C>G		3_prime_UTR	Exon 12 of 12	ENSP00000635974.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29183 AN: 151984 Hom.: 5881 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0900

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.120 AC: 54 AN: 450 Hom.: 1 Cov.: 0 AF XY: 0.119 AC XY: 32 AN XY: 270

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.121 AC: 50 AN: 412

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0714 AC: 2 AN: 28

Other (OTH) AF: 0.125 AC: 1 AN: 8

GnomAD4 genome AF: 0.192 AC: 29267 AN: 152102 Hom.: 5914 Cov.: 32 AF XY: 0.190 AC XY: 14154 AN XY: 74368

African (AFR) AF: 0.512 AC: 21197 AN: 41414

American (AMR) AF: 0.0890 AC: 1361 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3468

East Asian (EAS) AF: 0.0904 AC: 469 AN: 5188

South Asian (SAS) AF: 0.0937 AC: 452 AN: 4826

European-Finnish (FIN) AF: 0.135 AC: 1432 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0544 AC: 3702 AN: 68004

Other (OTH) AF: 0.155 AC: 328 AN: 2114

Alfa AF: 0.125 Hom.: 444

Bravo AF: 0.202

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Idiopathic basal ganglia calcification 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.98
DANN	Benign	0.48
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs6841; hg19: chr8-42274264; COSMIC: COSV60604921; COSMIC: COSV60604921;