rs147129009

Variant names:

• chr4-25662722-C-A
• rs147129009
• NM_006424.3:c.130C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-25662722-C-A
• chr4-25662722-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006424.3(SLC34A2):​c.130C>A​(p.Pro44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P44S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC34A2 NM_006424.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 0 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10388738).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A2	NM_006424.3	MANE Select	c.130C>A	p.Pro44Thr	missense	Exon 3 of 13	NP_006415.3	O95436-1
	SLC34A2	NM_001177998.2		c.127C>A	p.Pro43Thr	missense	Exon 3 of 13	NP_001171469.2	O95436-2
	SLC34A2	NM_001177999.2		c.127C>A	p.Pro43Thr	missense	Exon 3 of 13	NP_001171470.2	O95436-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A2	ENST00000382051.8	TSL:1 MANE Select	c.130C>A	p.Pro44Thr	missense	Exon 3 of 13	ENSP00000371483.3	O95436-1
	SLC34A2	ENST00000503434.5	TSL:1	c.127C>A	p.Pro43Thr	missense	Exon 3 of 13	ENSP00000423021.1	O95436-2
	SLC34A2	ENST00000504570.5	TSL:1	c.127C>A	p.Pro43Thr	missense	Exon 3 of 13	ENSP00000425501.1	O95436-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.49
DANN	Benign	0.90
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.027
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.041
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.82	P
Vest4		0.23
MutPred		0.23		Gain of glycosylation at T46 (P = 0.0452)
MVP		0.51
MPC		0.28
ClinPred		0.42	T
GERP RS		-0.75
Varity_R		0.050
gMVP		0.37
Mutation Taster		=93/7	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: rs147129009; hg19: chr4-25664344;