rs28591989

Variant names:

• chr9-137236430-A-C
• rs28591989
• NM_001177316.2:c.*14A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137236430-A-C
• chr9-137236430-A-T

Variant summary

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

The NM_001177316.2(SLC34A3):​c.*14A>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 0.408 in 1,534,196 control chromosomes in the GnomAD database, including 129,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12188 hom., cov: 33)
  • Exomes 𝑓: 0.41 (117661 hom.)
• Consequence: SLC34A3 NM_001177316.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -4.56
• Publications: 10 publications found

Genes affected

SLC34A3 (HGNC:20305): (solute carrier family 34 member 3) This gene encodes a member of SLC34A transporter family of proteins, and is expressed primarily in the kidney. It is involved in transporting phosphate into cells via sodium cotransport in the renal brush border membrane, and contributes to the maintenance of inorganic phosphate concentration in the kidney. Mutations in this gene are associated with hereditary hypophosphatemic rickets with hypercalciuria. Alternatively spliced transcript variants varying in the 5' UTR have been found for this gene.[provided by RefSeq, Apr 2010]

SLC34A3 Gene-Disease associations (from GenCC):

• hereditary hypophosphatemic rickets with hypercalciuria

  Inheritance: SD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 9-137236430-A-C is Benign according to our data. Variant chr9-137236430-A-C is described in ClinVar as Benign. ClinVar VariationId is 194276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177316.2. 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
	SLC34A3	NM_001177316.2	MANE Select	c.*14A>C		3_prime_UTR	Exon 13 of 13	NP_001170787.2	Q8N130
	SLC34A3	NM_001177317.2		c.*14A>C		3_prime_UTR	Exon 13 of 13	NP_001170788.2	Q8N130
	SLC34A3	NM_080877.3		c.*14A>C		3_prime_UTR	Exon 13 of 13	NP_543153.2	Q8N130

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	ENST00000673835.1	MANE Select	c.*14A>C		3_prime_UTR	Exon 13 of 13	ENSP00000501114.1	Q8N130
	SLC34A3	ENST00000361134.2	TSL:2	c.*14A>C		3_prime_UTR	Exon 13 of 13	ENSP00000355353.2	Q8N130
	SLC34A3	ENST00000538474.5	TSL:5	c.*14A>C		3_prime_UTR	Exon 13 of 13	ENSP00000442397.1	Q8N130

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60144 AN: 151946 Hom.: 12178 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.386

GnomAD2 exomes AF: 0.380 AC: 54111 AN: 142348 AF XY: 0.377

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.146

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.421

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.409 AC: 565204 AN: 1382132 Hom.: 117661 Cov.: 35 AF XY: 0.408 AC XY: 278301 AN XY: 682268

African (AFR) AF: 0.421 AC: 13266 AN: 31540

American (AMR) AF: 0.402 AC: 14331 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 10727 AN: 25148

East Asian (EAS) AF: 0.162 AC: 5776 AN: 35704

South Asian (SAS) AF: 0.355 AC: 28109 AN: 79188

European-Finnish (FIN) AF: 0.294 AC: 10125 AN: 34418

Middle Eastern (MID) AF: 0.318 AC: 1778 AN: 5594

European-Non Finnish (NFE) AF: 0.426 AC: 458541 AN: 1077076

Other (OTH) AF: 0.390 AC: 22551 AN: 57778

GnomAD4 genome AF: 0.396 AC: 60176 AN: 152064 Hom.: 12188 Cov.: 33 AF XY: 0.386 AC XY: 28722 AN XY: 74360

African (AFR) AF: 0.417 AC: 17305 AN: 41490

American (AMR) AF: 0.384 AC: 5875 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3470

East Asian (EAS) AF: 0.150 AC: 774 AN: 5152

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4820

European-Finnish (FIN) AF: 0.295 AC: 3133 AN: 10606

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28534 AN: 67916

Other (OTH) AF: 0.382 AC: 808 AN: 2116

Alfa AF: 0.319 Hom.: 1290

Bravo AF: 0.405

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.22
DANN	Benign	0.50
PhyloP100		-4.6
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs28591989;

hg19: chr9-140130882;

COSMIC: COSV61163671;

COSMIC: COSV61163671;