rs77319279

chr4-25667908-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006424.3(SLC34A2):c.552T>C(p.Ile184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,612,818 control chromosomes in the GnomAD database, including 788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (78 hom., cov: 32)
  • Exomes 𝑓: 0.028 (710 hom.)
• Consequence: SLC34A2 NM_006424.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.122

Genes affected

SLC34A2 (HGNC:11020): (solute carrier family 34 member 2) The protein encoded by this gene is a pH-sensitive sodium-dependent phosphate transporter. Phosphate uptake is increased at lower pH. Defects in this gene are a cause of pulmonary alveolar microlithiasis. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 4-25667908-T-C is Benign according to our data. Variant chr4-25667908-T-C is described in ClinVar as [Benign]. Clinvar id is 403455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-25667908-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.122 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.022 (3346/152292) while in subpopulation NFE AF= 0.0305 (2074/68026). AF 95% confidence interval is 0.0294. There are 78 homozygotes in gnomad4. There are 1666 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 78 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A2	NM_006424.3	c.552T>C	p.Ile184=	synonymous_variant	6/13	ENST00000382051.8
SLC34A2	NM_001177998.2	c.549T>C	p.Ile183=	synonymous_variant	6/13
SLC34A2	NM_001177999.2	c.549T>C	p.Ile183=	synonymous_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A2	ENST00000382051.8	c.552T>C	p.Ile184=	synonymous_variant	6/13	1	NM_006424.3	P4

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3346 AN: 152174 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.00666

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0320

GnomAD3 exomes AF: 0.0217 AC: 5446 AN: 251430 Hom.: 83 AF XY: 0.0220 AC XY: 2992 AN XY: 135888

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.0167

Gnomad ASJ exome AF: 0.0195

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00817

Gnomad FIN exome AF: 0.0335

Gnomad NFE exome AF: 0.0302

Gnomad OTH exome AF: 0.0272

GnomAD4 exome AF: 0.0277 AC: 40464 AN: 1460526 Hom.: 710 Cov.: 30 AF XY: 0.0271 AC XY: 19677 AN XY: 726624

Gnomad4 AFR exome AF: 0.00574

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00916

Gnomad4 FIN exome AF: 0.0345

Gnomad4 NFE exome AF: 0.0310

Gnomad4 OTH exome AF: 0.0271

GnomAD4 genome AF: 0.0220 AC: 3346 AN: 152292 Hom.: 78 Cov.: 32 AF XY: 0.0224 AC XY: 1666 AN XY: 74466

Gnomad4 AFR AF: 0.00667

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00685

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0259 Hom.: 21

Bravo AF: 0.0213

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.0347

EpiControl AF: 0.0341

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	4.5
Dann	Benign	0.76

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: rs77319279; hg19: chr4-25669530;