9-137236430-A-T

Position:

• chr9-137236430-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001177316.2(SLC34A3):​c.*14A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,534,680 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (6 hom.)
• Consequence: SLC34A3 NM_001177316.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.56

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-137236430-A-T is Benign according to our data. Variant chr9-137236430-A-T is described in ClinVar as [Benign]. Clinvar id is 1705043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A3	NM_001177316.2	c.*14A>T		3_prime_UTR_variant	13/13	ENST00000673835.1	NP_001170787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A3	ENST00000673835.1	c.*14A>T		3_prime_UTR_variant	13/13		NM_001177316.2	ENSP00000501114.1
SLC34A3	ENST00000361134.2	c.*14A>T		3_prime_UTR_variant	13/13	2		ENSP00000355353.2
SLC34A3	ENST00000538474.5	c.*14A>T		3_prime_UTR_variant	13/13	5		ENSP00000442397.1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 219 AN: 151984 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00253

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00148 AC: 210 AN: 142348 Hom.: 0 AF XY: 0.00148 AC XY: 113 AN XY: 76218

Gnomad AFR exome AF: 0.000360

Gnomad AMR exome AF: 0.000487

Gnomad ASJ exome AF: 0.000237

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00140

GnomAD4 exome AF: 0.00251 AC: 3474 AN: 1382578 Hom.: 6 Cov.: 35 AF XY: 0.00246 AC XY: 1682 AN XY: 682466

Gnomad4 AFR exome AF: 0.000729

Gnomad4 AMR exome AF: 0.000673

Gnomad4 ASJ exome AF: 0.000278

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.000232

Gnomad4 NFE exome AF: 0.00299

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00144 AC: 219 AN: 152102 Hom.: 0 Cov.: 33 AF XY: 0.00124 AC XY: 92 AN XY: 74380

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00253

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000855 Hom.: 1290

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 04, 2022

Variant summary: SLC34A3 c.*14A>T is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.0015 in 142348 control chromosomes, predominantly at a frequency of 0.0026 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC34A3 causing Hereditary Hypophosphatemic Rickets With Hypercalciuria phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.*14A>T in individuals affected with Hereditary Hypophosphatemic Rickets With Hypercalciuria and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.22
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs28591989; hg19: chr9-140130882;