4-25662622-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006424.3(SLC34A2):c.112+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,613,906 control chromosomes in the GnomAD database, including 3,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.059 (442 hom., cov: 32)
  • Exomes 𝑓: 0.046 (3239 hom.)
• Consequence: SLC34A2 NM_006424.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.17

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 4-25662622-G-A is Benign according to our data. Variant chr4-25662622-G-A is described in ClinVar as [Benign]. Clinvar id is 1600581.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-25662622-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A2	NM_006424.3	c.112+10G>A		intron_variant		ENST00000382051.8
SLC34A2	NM_001177998.2	c.112+10G>A		intron_variant
SLC34A2	NM_001177999.2	c.112+10G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A2	ENST00000382051.8	c.112+10G>A		intron_variant		1	NM_006424.3	P4

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8879 AN: 151996 Hom.: 439 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0642

GnomAD3 exomes AF: 0.0745 AC: 18733 AN: 251482 Hom.: 1304 AF XY: 0.0717 AC XY: 9748 AN XY: 135916

Gnomad AFR exome AF: 0.0672

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.0222

Gnomad EAS exome AF: 0.258

Gnomad SAS exome AF: 0.0958

Gnomad FIN exome AF: 0.0421

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0645

GnomAD4 exome AF: 0.0457 AC: 66811 AN: 1461792 Hom.: 3239 Cov.: 33 AF XY: 0.0464 AC XY: 33777 AN XY: 727198

Gnomad4 AFR exome AF: 0.0678

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.0979

Gnomad4 FIN exome AF: 0.0434

Gnomad4 NFE exome AF: 0.0297

Gnomad4 OTH exome AF: 0.0597

GnomAD4 genome AF: 0.0585 AC: 8901 AN: 152114 Hom.: 442 Cov.: 32 AF XY: 0.0626 AC XY: 4654 AN XY: 74348

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0300

Gnomad4 OTH AF: 0.0654

Alfa AF: 0.0224 Hom.: 16

Bravo AF: 0.0646

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.0030
Dann	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs4697597; hg19: chr4-25664244; COSMIC: COSV65941723; COSMIC: COSV65941723;