NM_001177316.2:c.273C>T

Variant names:

• chr9-137232672-C-T
• rs145677050
• NM_001177316.2:c.273C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001177316.2(SLC34A3):​c.273C>T​(p.Asp91Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,612,850 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (30 hom.)
• Consequence: SLC34A3 NM_001177316.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.241
• Publications: 0 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: AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 9-137232672-C-T is Benign according to our data. Variant chr9-137232672-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 284536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.241 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00359 (547/152348) while in subpopulation NFE AF = 0.00559 (380/68014). AF 95% confidence interval is 0.00512. There are 1 homozygotes in GnomAd4. There are 275 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 30 AR,SD gene

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.273C>T	p.Asp91Asp	synonymous	Exon 4 of 13	NP_001170787.2	Q8N130
	SLC34A3	NM_001177317.2		c.273C>T	p.Asp91Asp	synonymous	Exon 4 of 13	NP_001170788.2	Q8N130
	SLC34A3	NM_080877.3		c.273C>T	p.Asp91Asp	synonymous	Exon 4 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.273C>T	p.Asp91Asp	synonymous	Exon 4 of 13	ENSP00000501114.1	Q8N130
	SLC34A3	ENST00000361134.2	TSL:2	c.273C>T	p.Asp91Asp	synonymous	Exon 4 of 13	ENSP00000355353.2	Q8N130
	SLC34A3	ENST00000538474.5	TSL:5	c.273C>T	p.Asp91Asp	synonymous	Exon 4 of 13	ENSP00000442397.1	Q8N130

Frequencies

GnomAD3 genomes AF: 0.00359 AC: 547 AN: 152230 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00559

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00430 AC: 1077 AN: 250250 AF XY: 0.00444

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.000998

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00698

Gnomad NFE exome AF: 0.00570

Gnomad OTH exome AF: 0.00688

GnomAD4 exome AF: 0.00541 AC: 7903 AN: 1460502 Hom.: 30 Cov.: 39 AF XY: 0.00541 AC XY: 3932 AN XY: 726548

African (AFR) AF: 0.000538 AC: 18 AN: 33476

American (AMR) AF: 0.00387 AC: 173 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 33 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00379 AC: 327 AN: 86258

European-Finnish (FIN) AF: 0.00696 AC: 363 AN: 52160

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00598 AC: 6651 AN: 1111920

Other (OTH) AF: 0.00552 AC: 333 AN: 60374

GnomAD4 genome AF: 0.00359 AC: 547 AN: 152348 Hom.: 1 Cov.: 33 AF XY: 0.00369 AC XY: 275 AN XY: 74496

African (AFR) AF: 0.000625 AC: 26 AN: 41590

American (AMR) AF: 0.00385 AC: 59 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4830

European-Finnish (FIN) AF: 0.00518 AC: 55 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00559 AC: 380 AN: 68014

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00411 Hom.: 1

Bravo AF: 0.00342

EpiCase AF: 0.00469

EpiControl AF: 0.00433

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	1	Autosomal recessive hypophosphatemic bone disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		0.24
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs145677050; hg19: chr9-140127124; COSMIC: COSV63187857; COSMIC: COSV63187857;