5-177385731-G-C

Position:

• chr5-177385731-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003052.5(SLC34A1):​c.-11G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,604,332 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (7 hom.)
• Consequence: SLC34A1 NM_003052.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51

Genes affected

SLC34A1 (HGNC:11019): (solute carrier family 34 member 1) Enables sodium:phosphate symporter activity. Involved in several processes, including phosphate ion homeostasis; phosphate ion transport; and response to lead ion. Located in several cellular components, including apical plasma membrane; mitotic spindle; and nuclear speck. Implicated in several diseases, including Fanconi syndrome (multiple); chronic kidney disease; hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; and nephrolithiasis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-177385731-G-C is Benign according to our data. Variant chr5-177385731-G-C is described in ClinVar as [Benign]. Clinvar id is 352952.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00122 (185/152230) while in subpopulation AFR AF= 0.00181 (75/41550). AF 95% confidence interval is 0.00148. There are 4 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A1	NM_003052.5	c.-11G>C		5_prime_UTR_variant	2/13	ENST00000324417.6
SLC34A1	NM_001167579.2	c.-11G>C		5_prime_UTR_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A1	ENST00000324417.6	c.-11G>C		5_prime_UTR_variant	2/13	1	NM_003052.5	P1
SLC34A1	ENST00000504577.5	c.-11G>C		5_prime_UTR_variant	2/4	4
SLC34A1	ENST00000512593.5	c.-11G>C		5_prime_UTR_variant	2/9	2
SLC34A1	ENST00000507685.5	n.74G>C		non_coding_transcript_exon_variant	2/10	2

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 185 AN: 152112 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00108 AC: 263 AN: 242614 Hom.: 0 AF XY: 0.00107 AC XY: 140 AN XY: 131098

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00254

Gnomad ASJ exome AF: 0.000413

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000641

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.00239

GnomAD4 exome AF: 0.00101 AC: 1473 AN: 1452102 Hom.: 7 Cov.: 31 AF XY: 0.00101 AC XY: 730 AN XY: 722566

Gnomad4 AFR exome AF: 0.00144

Gnomad4 AMR exome AF: 0.00285

Gnomad4 ASJ exome AF: 0.000310

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000927

Gnomad4 FIN exome AF: 0.0000377

Gnomad4 NFE exome AF: 0.000890

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00122 AC: 185 AN: 152230 Hom.: 4 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74428

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000971

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00100 Hom.: 0

Bravo AF: 0.00147

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypophosphatemic nephrolithiasis/osteoporosis 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs368569333; hg19: chr5-176812732;