4-25664197-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006424.3(SLC34A2):c.251-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 750,694 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000062 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC34A2 NM_006424.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004623
• Clinical Significance: Likely benign criteria provided, single submitter 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-25664197-T-C is Benign according to our data. Variant chr4-25664197-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 789940.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 129726 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000894

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000235

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000489

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000426 AC: 32 AN: 750694 Hom.: 0 Cov.: 23 AF XY: 0.0000513 AC XY: 20 AN XY: 390220

Gnomad4 AFR exome AF: 0.0000558

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000276

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000516

Gnomad4 OTH exome AF: 0.0000955

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000616 AC: 8 AN: 129808 Hom.: 0 Cov.: 31 AF XY: 0.0000479 AC XY: 3 AN XY: 62666

Gnomad4 AFR AF: 0.0000892

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000235

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000124

Gnomad4 NFE AF: 0.0000489

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00162 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.59
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000046
dbscSNV1_RF	Benign	0.024
SpliceAI score (max)		0.030		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;