rs12505556

Variant names:

• chr4-25675360-C-A
• rs12505556
• NM_006424.3:c.1458+731C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-25675360-C-A
• chr4-25675360-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006424.3(SLC34A2):​c.1458+731C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,228 control chromosomes in the GnomAD database, including 2,520 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2520 hom., cov: 33)
• Consequence: SLC34A2 NM_006424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A2	NM_006424.3	MANE Select	c.1458+731C>A		intron	N/A	NP_006415.3	O95436-1
	SLC34A2	NM_001177998.2		c.1455+731C>A		intron	N/A	NP_001171469.2	O95436-2
	SLC34A2	NM_001177999.2		c.1455+731C>A		intron	N/A	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.1458+731C>A		intron	N/A	ENSP00000371483.3	O95436-1
	SLC34A2	ENST00000503434.5	TSL:1	c.1455+731C>A		intron	N/A	ENSP00000423021.1	O95436-2
	SLC34A2	ENST00000504570.5	TSL:1	c.1455+731C>A		intron	N/A	ENSP00000425501.1	O95436-2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23906 AN: 152110 Hom.: 2514 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23930 AN: 152228 Hom.: 2520 Cov.: 33 AF XY: 0.162 AC XY: 12095 AN XY: 74436

African (AFR) AF: 0.136 AC: 5631 AN: 41542

American (AMR) AF: 0.230 AC: 3514 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2953 AN: 5164

South Asian (SAS) AF: 0.168 AC: 814 AN: 4832

European-Finnish (FIN) AF: 0.151 AC: 1598 AN: 10604

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8247 AN: 68012

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.140 Hom.: 3411

Bravo AF: 0.169

Asia WGS AF: 0.362 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.80
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs12505556; hg19: chr4-25676982;