9-137233273-C-T

Variant names:

• chr9-137233273-C-T
• rs34796681
• NM_001177316.2:c.625C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001177316.2(SLC34A3):​c.625C>T​(p.Leu209Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,584,374 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (37 hom.)
• Consequence: SLC34A3 NM_001177316.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.214
• 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: SD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-137233273-C-T is Benign according to our data. Variant chr9-137233273-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 504908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00413 (628/152242) while in subpopulation NFE AF = 0.00776 (528/68002). AF 95% confidence interval is 0.00722. There are 1 homozygotes in GnomAd4. There are 276 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 37 SD,AR 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	NM_001177316.2	MANE Select	c.625C>T	p.Leu209Leu	synonymous	Exon 7 of 13	NP_001170787.2
	SLC34A3	NM_001177317.2		c.625C>T	p.Leu209Leu	synonymous	Exon 7 of 13	NP_001170788.2
	SLC34A3	NM_080877.3		c.625C>T	p.Leu209Leu	synonymous	Exon 7 of 13	NP_543153.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	ENST00000673835.1	MANE Select	c.625C>T	p.Leu209Leu	synonymous	Exon 7 of 13	ENSP00000501114.1
	SLC34A3	ENST00000361134.2	TSL:2	c.625C>T	p.Leu209Leu	synonymous	Exon 7 of 13	ENSP00000355353.2
	SLC34A3	ENST00000538474.5	TSL:5	c.625C>T	p.Leu209Leu	synonymous	Exon 7 of 13	ENSP00000442397.1

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 628 AN: 152124 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00776

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00365 AC: 724 AN: 198322 AF XY: 0.00371

Gnomad AFR exome AF: 0.000784

Gnomad AMR exome AF: 0.000732

Gnomad ASJ exome AF: 0.000331

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000635

Gnomad NFE exome AF: 0.00775

Gnomad OTH exome AF: 0.00448

GnomAD4 exome AF: 0.00630 AC: 9019 AN: 1432132 Hom.: 37 Cov.: 36 AF XY: 0.00592 AC XY: 4203 AN XY: 710152

African (AFR) AF: 0.00143 AC: 47 AN: 32762

American (AMR) AF: 0.000827 AC: 34 AN: 41102

Ashkenazi Jewish (ASJ) AF: 0.000391 AC: 10 AN: 25592

East Asian (EAS) AF: 0.00 AC: 0 AN: 37910

South Asian (SAS) AF: 0.000133 AC: 11 AN: 82780

European-Finnish (FIN) AF: 0.00147 AC: 73 AN: 49660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00784 AC: 8604 AN: 1097482

Other (OTH) AF: 0.00406 AC: 240 AN: 59130

GnomAD4 genome AF: 0.00413 AC: 628 AN: 152242 Hom.: 1 Cov.: 32 AF XY: 0.00371 AC XY: 276 AN XY: 74438

African (AFR) AF: 0.00142 AC: 59 AN: 41544

American (AMR) AF: 0.00157 AC: 24 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00776 AC: 528 AN: 68002

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00597 Hom.: 3

Bravo AF: 0.00408

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.95
PhyloP100		0.21
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: rs34796681; hg19: chr9-140127725;