4-25662542-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_006424.3(SLC34A2):c.42C>T(p.Pro14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,614,052 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: SLC34A2 NM_006424.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-25662542-C-T is Benign according to our data. Variant chr4-25662542-C-T is described in ClinVar as [Benign]. Clinvar id is 773187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.354 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0028 (426/152170) while in subpopulation AFR AF= 0.00963 (400/41526). AF 95% confidence interval is 0.00885. There are 1 homozygotes in gnomad4. There are 196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A2	NM_006424.3	c.42C>T	p.Pro14=	synonymous_variant	2/13	ENST00000382051.8
SLC34A2	NM_001177998.2	c.42C>T	p.Pro14=	synonymous_variant	2/13
SLC34A2	NM_001177999.2	c.42C>T	p.Pro14=	synonymous_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A2	ENST00000382051.8	c.42C>T	p.Pro14=	synonymous_variant	2/13	1	NM_006424.3	P4

Frequencies

GnomAD3 genomes AF: 0.00280 AC: 426 AN: 152052 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000605 AC: 152 AN: 251444 Hom.: 2 AF XY: 0.000500 AC XY: 68 AN XY: 135900

Gnomad AFR exome AF: 0.00867

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000257 AC: 376 AN: 1461882 Hom.: 2 Cov.: 33 AF XY: 0.000221 AC XY: 161 AN XY: 727242

Gnomad4 AFR exome AF: 0.00935

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.000629

GnomAD4 genome AF: 0.00280 AC: 426 AN: 152170 Hom.: 1 Cov.: 32 AF XY: 0.00263 AC XY: 196 AN XY: 74398

Gnomad4 AFR AF: 0.00963

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00301

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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 08, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	5.7
Dann	Benign	0.49

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: rs61740664; hg19: chr4-25664164;