6-25779164-A-G

Variant names:

• chr6-25779164-A-G
• rs9358890
• NM_005495.3:c.1470A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005495.3(SLC17A4):​c.1470A>G​(p.Lys490Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,613,766 control chromosomes in the GnomAD database, including 12,323 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.077 (1152 hom., cov: 32)
  • Exomes 𝑓: 0.074 (11171 hom.)
• Consequence: SLC17A4 NM_005495.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 17 publications found

Genes affected

SLC17A4 (HGNC:10932): (solute carrier family 17 member 4) Phosphate homeostasis is maintained by regulating intake, intestinal absorption, bone deposition and resorption, and renal excretion of phosphate. The central molecule in the control of phosphate excretion from the kidney is the sodium/phosphate cotransporter NPT1 (SLC17A1; MIM 182308), which is located in the renal proximal tubule. NPT1 uses the transmembrane electrochemical potential gradient of sodium to transport phosphate across the cell membrane. SLC17A4 is a similar sodium/phosphate cotransporter in the intestinal mucosa that plays an important role in the absorption of phosphate from the intestine (summary by Shibui et al., 1999 [PubMed 10319585]).[supplied by OMIM, Feb 2011]

SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.382 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A4	NM_005495.3	c.1470A>G	p.Lys490Lys	synonymous_variant	Exon 12 of 12	ENST00000377905.9	NP_005486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A4	ENST00000377905.9	c.1470A>G	p.Lys490Lys	synonymous_variant	Exon 12 of 12	1	NM_005495.3	ENSP00000367137.4
SLC17A4	ENST00000439485.6	c.1308A>G	p.Lys436Lys	synonymous_variant	Exon 13 of 13	5		ENSP00000391345.3
SLC17A4	ENST00000397076.2	c.*1027A>G		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000380266.2

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11732 AN: 152130 Hom.: 1146 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0915

GnomAD2 exomes AF: 0.125 AC: 31443 AN: 251124 AF XY: 0.121

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.0593

Gnomad EAS exome AF: 0.501

Gnomad FIN exome AF: 0.0321

Gnomad NFE exome AF: 0.0457

Gnomad OTH exome AF: 0.0943

GnomAD4 exome AF: 0.0745 AC: 108883 AN: 1461516 Hom.: 11171 Cov.: 31 AF XY: 0.0771 AC XY: 56030 AN XY: 727040

African (AFR) AF: 0.0465 AC: 1555 AN: 33460

American (AMR) AF: 0.243 AC: 10880 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0601 AC: 1570 AN: 26120

East Asian (EAS) AF: 0.565 AC: 22427 AN: 39694

South Asian (SAS) AF: 0.180 AC: 15497 AN: 86236

European-Finnish (FIN) AF: 0.0319 AC: 1704 AN: 53418

Middle Eastern (MID) AF: 0.0804 AC: 463 AN: 5760

European-Non Finnish (NFE) AF: 0.0446 AC: 49619 AN: 1111754

Other (OTH) AF: 0.0856 AC: 5168 AN: 60374

GnomAD4 genome AF: 0.0772 AC: 11748 AN: 152250 Hom.: 1152 Cov.: 32 AF XY: 0.0833 AC XY: 6204 AN XY: 74442

African (AFR) AF: 0.0479 AC: 1993 AN: 41566

American (AMR) AF: 0.151 AC: 2299 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0570 AC: 198 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2589 AN: 5166

South Asian (SAS) AF: 0.199 AC: 960 AN: 4822

European-Finnish (FIN) AF: 0.0302 AC: 321 AN: 10618

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0460 AC: 3126 AN: 68020

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.0662 Hom.: 2082

Bravo AF: 0.0866

Asia WGS AF: 0.307 AC: 1065 AN: 3478

EpiCase AF: 0.0540

EpiControl AF: 0.0483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		-0.38
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: rs9358890; hg19: chr6-25779392; COSMIC: COSV55082588; COSMIC: COSV55082588;