4-25662780-C-A

Variant names:

• chr4-25662780-C-A
• NM_006424.3:c.188C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006424.3(SLC34A2):​c.188C>A​(p.Pro63His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC34A2 NM_006424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.306

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07681206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.188C>A	p.Pro63His	missense_variant	Exon 3 of 13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.185C>A	p.Pro62His	missense_variant	Exon 3 of 13		NP_001171469.2
SLC34A2	NM_001177999.2	c.185C>A	p.Pro62His	missense_variant	Exon 3 of 13		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.188C>A	p.Pro63His	missense_variant	Exon 3 of 13	1	NM_006424.3	ENSP00000371483.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jan 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.188C>A (p.P63H) alteration is located in exon 3 (coding exon 2) of the SLC34A2 gene. This alteration results from a C to A substitution at nucleotide position 188, causing the proline (P) at amino acid position 63 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.095	.;.;.;T;.;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.31	.;T;.;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.077	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;.;.;L;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.6	.;D;D;D;D;D
REVEL	Benign	0.040
Sift	Benign	0.074	.;T;T;T;T;T
Sift4G	Benign	0.17	.;T;T;T;T;T
Polyphen		0.0080	B;.;B;B;B;.
Vest4		0.22, 0.22, 0.22
MutPred		0.26		.;.;.;Loss of sheet (P = 0.0315);.;Loss of sheet (P = 0.0315);
MVP		0.68
MPC		0.28
ClinPred		0.081	T
GERP RS		2.7
Varity_R		0.089
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-25664402;