4-25664197-T-G

Position:

• chr4-25664197-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_006424.3(SLC34A2):​c.251-5T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.00083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC34A2 NM_006424.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.005715
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.716

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_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-25664197-T-G is Benign according to our data. Variant chr4-25664197-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3352718.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.251-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.248-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001171469.2
SLC34A2	NM_001177999.2	c.248-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.251-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006424.3	ENSP00000371483	P4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000829 AC: 622 AN: 750414 Hom.: 0 Cov.: 23 AF XY: 0.000774 AC XY: 302 AN XY: 390102

Gnomad4 AFR exome AF: 0.000670

Gnomad4 AMR exome AF: 0.0000257

Gnomad4 ASJ exome AF: 0.000358

Gnomad4 EAS exome AF: 0.000123

Gnomad4 SAS exome AF: 0.000166

Gnomad4 FIN exome AF: 0.0000483

Gnomad4 NFE exome AF: 0.00110

Gnomad4 OTH exome AF: 0.000923

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC34A2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 19, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0057
dbscSNV1_RF	Benign	0.10
SpliceAI score (max)		0.080		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: rs1204780387; hg19: chr4-25665819;