rs137853142

Positions:

• chr4-25664267-G-A
• chr4-25664267-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006424.3(SLC34A2):​c.316G>A​(p.Gly106Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SLC34A2 NM_006424.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.76

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.982

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.316G>A	p.Gly106Arg	missense_variant	4/13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.313G>A	p.Gly105Arg	missense_variant	4/13		NP_001171469.2
SLC34A2	NM_001177999.2	c.313G>A	p.Gly105Arg	missense_variant	4/13		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.316G>A	p.Gly106Arg	missense_variant	4/13	1	NM_006424.3	ENSP00000371483.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251480 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461618 Hom.: 0 Cov.: 34 AF XY: 0.0000220 AC XY: 16 AN XY: 727150

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000602 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.69	.;.;.;D;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;.;D;D;D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.5	.;.;.;M;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.1	.;D;D;D;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0060	.;D;T;T;T;D
Sift4G	Uncertain	0.034	.;D;T;T;T;D
Polyphen		1.0	D;.;D;D;D;.
Vest4		0.94, 0.94, 0.94
MutPred		0.94		.;.;.;Gain of MoRF binding (P = 0.0333);.;Gain of MoRF binding (P = 0.0333);
MVP		0.89
MPC		0.86
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.73
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs137853142; hg19: chr4-25665889; COSMIC: COSV65942208; COSMIC: COSV65942208;