NM_001177316.2:c.175+123C>T

Variant names:

• chr9-137232284-C-T
• rs111532084
• NM_001177316.2:c.175+123C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001177316.2(SLC34A3):​c.175+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 989,004 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (60 hom., cov: 33)
  • Exomes 𝑓: 0.029 (463 hom.)
• Consequence: SLC34A3 NM_001177316.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-137232284-C-T is Benign according to our data. Variant chr9-137232284-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 496510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0236 (3598/152306) while in subpopulation NFE AF = 0.0368 (2501/68012). AF 95% confidence interval is 0.0356. There are 60 homozygotes in GnomAd4. There are 1670 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 60 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	NM_001177316.2	MANE Select	c.175+123C>T		intron	N/A	NP_001170787.2	Q8N130
	SLC34A3	NM_001177317.2		c.175+123C>T		intron	N/A	NP_001170788.2	Q8N130
	SLC34A3	NM_080877.3		c.175+123C>T		intron	N/A	NP_543153.2	Q8N130

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	ENST00000673835.1	MANE Select	c.175+123C>T		intron	N/A	ENSP00000501114.1	Q8N130
	SLC34A3	ENST00000361134.2	TSL:2	c.175+123C>T		intron	N/A	ENSP00000355353.2	Q8N130
	SLC34A3	ENST00000538474.5	TSL:5	c.175+123C>T		intron	N/A	ENSP00000442397.1	Q8N130

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3596 AN: 152188 Hom.: 60 Cov.: 33

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0368

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0290 AC: 24258 AN: 836698 Hom.: 463 AF XY: 0.0292 AC XY: 12656 AN XY: 433256

African (AFR) AF: 0.00555 AC: 118 AN: 21244

American (AMR) AF: 0.0180 AC: 678 AN: 37698

Ashkenazi Jewish (ASJ) AF: 0.0327 AC: 639 AN: 19516

East Asian (EAS) AF: 0.0000562 AC: 2 AN: 35596

South Asian (SAS) AF: 0.0221 AC: 1480 AN: 67082

European-Finnish (FIN) AF: 0.0190 AC: 718 AN: 37698

Middle Eastern (MID) AF: 0.0223 AC: 67 AN: 3006

European-Non Finnish (NFE) AF: 0.0338 AC: 19450 AN: 575380

Other (OTH) AF: 0.0280 AC: 1106 AN: 39478

GnomAD4 genome AF: 0.0236 AC: 3598 AN: 152306 Hom.: 60 Cov.: 33 AF XY: 0.0224 AC XY: 1670 AN XY: 74476

African (AFR) AF: 0.00611 AC: 254 AN: 41570

American (AMR) AF: 0.0196 AC: 300 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4828

European-Finnish (FIN) AF: 0.0156 AC: 166 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0368 AC: 2501 AN: 68012

Other (OTH) AF: 0.0279 AC: 59 AN: 2116

Alfa AF: 0.0297 Hom.: 10

Bravo AF: 0.0231

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.49
PhyloP100		-1.4
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: rs111532084; hg19: chr9-140126736;