NM_001257180.2:c.*263A>C

Variant names:

• chr8-42417540-T-G
• rs145543019
• NM_001257180.2:c.*263A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001257180.2(SLC20A2):​c.*263A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 268,956 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (3 hom.)
• Consequence: SLC20A2 NM_001257180.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 8-42417540-T-G is Benign according to our data. Variant chr8-42417540-T-G is described in ClinVar as Benign. ClinVar VariationId is 363062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00408 (618/151488) while in subpopulation SAS AF = 0.0083 (40/4820). AF 95% confidence interval is 0.00626. There are 6 homozygotes in GnomAd4. There are 282 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 618 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.*263A>C		3_prime_UTR	Exon 11 of 11	NP_001244109.1	A0A384MR38
	SLC20A2	NM_001257181.2		c.*263A>C		3_prime_UTR	Exon 11 of 11	NP_001244110.1	Q08357
	SLC20A2	NM_006749.5		c.*263A>C		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.*263A>C		3_prime_UTR	Exon 11 of 11	ENSP00000429754.1	Q08357
	SLC20A2	ENST00000342228.7	TSL:1	c.*263A>C		3_prime_UTR	Exon 11 of 11	ENSP00000340465.3	Q08357
	SLC20A2	ENST00000965915.1		c.*263A>C		3_prime_UTR	Exon 12 of 12	ENSP00000635974.1

Frequencies

GnomAD3 genomes AF: 0.00408 AC: 617 AN: 151370 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00675

Gnomad OTH AF: 0.00385

GnomAD4 exome AF: 0.00546 AC: 641 AN: 117468 Hom.: 3 Cov.: 0 AF XY: 0.00582 AC XY: 350 AN XY: 60184

African (AFR) AF: 0.00107 AC: 6 AN: 5614

American (AMR) AF: 0.00355 AC: 25 AN: 7048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4540

East Asian (EAS) AF: 0.00 AC: 0 AN: 10402

South Asian (SAS) AF: 0.0107 AC: 55 AN: 5160

European-Finnish (FIN) AF: 0.00383 AC: 20 AN: 5216

Middle Eastern (MID) AF: 0.0105 AC: 6 AN: 570

European-Non Finnish (NFE) AF: 0.00708 AC: 507 AN: 71582

Other (OTH) AF: 0.00300 AC: 22 AN: 7336

GnomAD4 genome AF: 0.00408 AC: 618 AN: 151488 Hom.: 6 Cov.: 32 AF XY: 0.00381 AC XY: 282 AN XY: 74072

African (AFR) AF: 0.00118 AC: 49 AN: 41490

American (AMR) AF: 0.00197 AC: 30 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00830 AC: 40 AN: 4820

European-Finnish (FIN) AF: 0.00255 AC: 27 AN: 10592

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00675 AC: 455 AN: 67382

Other (OTH) AF: 0.00381 AC: 8 AN: 2102

Alfa AF: 0.00631 Hom.: 2

Bravo AF: 0.00367

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

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	-0.39
CADD	Benign	5.3
DANN	Benign	0.79
PhyloP100		0.35
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: rs145543019; hg19: chr8-42275058;