rs77319279

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006424.3(SLC34A2):c.552T>C(p.Ile184Ile) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.122

Publications

5 publications found

Variant links:

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]

SLC34A2 Gene-Disease associations (from GenCC):

pulmonary alveolar microlithiasis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

SLC34A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 78 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A2	NM_006424.3 link	c.552T>C	p.Ile184Ile	synonymous_variant	Exon 6 of 13	ENST00000382051.8	NP_006415.3	O95436-1
SLC34A2	NM_001177998.2 link	c.549T>C	p.Ile183Ile	synonymous_variant	Exon 6 of 13		NP_001171469.2	O95436-2
SLC34A2	NM_001177999.2 link	c.549T>C	p.Ile183Ile	synonymous_variant	Exon 6 of 13		NP_001171470.2	O95436-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8 link	c.552T>C	p.Ile184Ile	synonymous_variant	Exon 6 of 13	1	NM_006424.3	ENSP00000371483.3		O95436-1

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3346

AN:

152174

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0217

AC:

5446

AN:

251430

AF XY:

0.0220

show subpopulations

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 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.:

AF XY:

0.0271

AC XY:

19677

AN XY:

726624

show subpopulations

African (AFR)

AF:

0.00574

AC:

192

AN:

33452

American (AMR)

AF:

0.0169

AC:

756

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0189

AC:

493

AN:

26124

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.00916

AC:

790

AN:

86226

European-Finnish (FIN)

AF:

0.0345

AC:

1842

AN:

53418

Middle Eastern (MID)

AF:

0.0517

AC:

298

AN:

5760

European-Non Finnish (NFE)

AF:

0.0310

AC:

34454

AN:

1110798

Other (OTH)

AF:

0.0271

AC:

1637

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2005

4010

6015

8020

10025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0220

AC:

3346

AN:

152292

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

1666

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00667

AC:

277

AN:

41560

American (AMR)

AF:

0.0255

AC:

390

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00685

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0353

AC:

375

AN:

10614

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0305

AC:

2074

AN:

68026

Other (OTH)

AF:

0.0317

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

160

319

479

638

798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0270

Hom.:

109

Bravo

AF:

0.0213

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0347

EpiControl

AF:

0.0341

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.5

(source)

DANN

Benign

0.76

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs77319279

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over