rs3796777

Variant names:

• chr4-25672572-T-C
• rs3796777
• NM_006424.3:c.1049-515T>C

Variant summary

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

The NM_006424.3(SLC34A2):​c.1049-515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,084 control chromosomes in the GnomAD database, including 3,784 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 0.20 (3784 hom., cov: 32)
• Consequence: SLC34A2 NM_006424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 4 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A2	NM_006424.3	MANE Select	c.1049-515T>C		intron	N/A	NP_006415.3
	SLC34A2	NM_001177998.2		c.1046-515T>C		intron	N/A	NP_001171469.2
	SLC34A2	NM_001177999.2		c.1046-515T>C		intron	N/A	NP_001171470.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A2	ENST00000382051.8	TSL:1 MANE Select	c.1049-515T>C		intron	N/A	ENSP00000371483.3
	SLC34A2	ENST00000503434.5	TSL:1	c.1046-515T>C		intron	N/A	ENSP00000423021.1
	SLC34A2	ENST00000504570.5	TSL:1	c.1046-515T>C		intron	N/A	ENSP00000425501.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30900 AN: 151966 Hom.: 3767 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.204 AC: 30958 AN: 152084 Hom.: 3784 Cov.: 32 AF XY: 0.204 AC XY: 15160 AN XY: 74342

African (AFR) AF: 0.331 AC: 13735 AN: 41444

American (AMR) AF: 0.203 AC: 3097 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1705 AN: 5160

South Asian (SAS) AF: 0.180 AC: 870 AN: 4822

European-Finnish (FIN) AF: 0.0997 AC: 1056 AN: 10594

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9273 AN: 67990

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.159 Hom.: 9072

Bravo AF: 0.215

Asia WGS AF: 0.250 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.60
PhyloP100		-0.82
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: rs3796777; hg19: chr4-25674194;