NM_006424.3:c.1901A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006424.3(SLC34A2):c.1901A>G(p.Asp634Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,613,476 control chromosomes in the GnomAD database, including 582,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59666 hom., cov: 34)

Exomes 𝑓: 0.84 ( 522873 hom. )

Consequence

SLC34A2
NM_006424.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.01

Publications

27 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.6177256E-7).

BP6

Variant 4-25676577-A-G is Benign according to our data. Variant chr4-25676577-A-G is described in ClinVar as Benign. ClinVar VariationId is 403456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC34A2	NM_006424.3	MANE Select	c.1901A>G	p.Asp634Gly	missense	Exon 13 of 13	NP_006415.3
SLC34A2	NM_001177998.2		c.1898A>G	p.Asp633Gly	missense	Exon 13 of 13	NP_001171469.2
SLC34A2	NM_001177999.2		c.1898A>G	p.Asp633Gly	missense	Exon 13 of 13	NP_001171470.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC34A2	ENST00000382051.8	TSL:1 MANE Select	c.1901A>G	p.Asp634Gly	missense	Exon 13 of 13	ENSP00000371483.3
SLC34A2	ENST00000503434.5	TSL:1	c.1898A>G	p.Asp633Gly	missense	Exon 13 of 13	ENSP00000423021.1
SLC34A2	ENST00000504570.5	TSL:1	c.1898A>G	p.Asp633Gly	missense	Exon 13 of 13	ENSP00000425501.1

Frequencies

GnomAD3 genomes

AF:

0.883

AC:

134319

AN:

152132

Hom.:

59603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.963

Gnomad AMI

AF:

0.786

Gnomad AMR

AF:

0.853

Gnomad ASJ

AF:

0.787

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.811

Gnomad FIN

AF:

0.908

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.841

Gnomad OTH

AF:

0.864

GnomAD2 exomes

AF:

0.862

AC:

215711

AN:

250268

AF XY:

0.855

show subpopulations

Gnomad AFR exome

AF:

0.968

Gnomad AMR exome

AF:

0.865

Gnomad ASJ exome

AF:

0.777

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.907

Gnomad NFE exome

AF:

0.841

Gnomad OTH exome

AF:

0.841

GnomAD4 exome

AF:

0.845

AC:

1234431

AN:

1461226

Hom.:

522873

Cov.:

AF XY:

0.843

AC XY:

612623

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.967

AC:

32370

AN:

33474

American (AMR)

AF:

0.866

AC:

38708

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.789

AC:

20615

AN:

26126

East Asian (EAS)

AF:

0.999

AC:

39660

AN:

39690

South Asian (SAS)

AF:

0.798

AC:

68790

AN:

86252

European-Finnish (FIN)

AF:

0.907

AC:

48340

AN:

53312

Middle Eastern (MID)

AF:

0.767

AC:

4419

AN:

5762

European-Non Finnish (NFE)

AF:

0.837

AC:

930666

AN:

1111566

Other (OTH)

AF:

0.843

AC:

50863

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

12060

24119

36179

48238

60298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21100

42200

63300

84400

105500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.883

AC:

134443

AN:

152250

Hom.:

59666

Cov.:

AF XY:

0.883

AC XY:

65728

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.963

AC:

40018

AN:

41560

American (AMR)

AF:

0.853

AC:

13051

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

2731

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5155

AN:

5164

South Asian (SAS)

AF:

0.811

AC:

3909

AN:

4822

European-Finnish (FIN)

AF:

0.908

AC:

9637

AN:

10608

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.841

AC:

57183

AN:

68006

Other (OTH)

AF:

0.866

AC:

1827

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

819

1639

2458

3278

4097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.849

Hom.:

60538

Bravo

AF:

0.884

TwinsUK

AF:

0.838

AC:

3107

ALSPAC

AF:

0.832

AC:

3207

ESP6500AA

AF:

0.961

AC:

4236

ESP6500EA

AF:

0.832

AC:

7157

ExAC

AF:

0.863

AC:

104785

Asia WGS

AF:

0.920

AC:

3197

AN:

3478

EpiCase

AF:

0.830

EpiControl

AF:

0.827

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

PULMONARY ALVEOLAR MICROLITHIASIS (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.015

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.24

MetaRNN

Benign

6.6e-7

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.6

PhyloP100

2.0

PrimateAI

Benign

0.29

PROVEAN

Benign

1.9

REVEL

Benign

0.059

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.077

MPC

0.31

ClinPred

0.00098

GERP RS

5.0

Varity_R

0.064

gMVP

0.40

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over