chr4-25664241-G-T

Position:

• chr4-25664241-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006424.3(SLC34A2):​c.290G>T​(p.Gly97Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC34A2 NM_006424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.290G>T	p.Gly97Val	missense_variant	4/13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.287G>T	p.Gly96Val	missense_variant	4/13		NP_001171469.2
SLC34A2	NM_001177999.2	c.287G>T	p.Gly96Val	missense_variant	4/13		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.290G>T	p.Gly97Val	missense_variant	4/13	1	NM_006424.3	ENSP00000371483	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.290G>T (p.G97V) alteration is located in exon 4 (coding exon 3) of the SLC34A2 gene. This alteration results from a G to T substitution at nucleotide position 290, causing the glycine (G) at amino acid position 97 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	.;.;.;T;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	.;T;.;T;T;T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.6	.;.;.;M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.3	.;D;D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.023	.;D;T;T;T;D
Sift4G	Benign	0.083	.;T;T;T;T;T
Polyphen		0.97	D;.;D;P;D;.
Vest4		0.73, 0.72
MutPred		0.52		.;.;.;Loss of methylation at R100 (P = 0.1092);.;Loss of methylation at R100 (P = 0.1092);
MVP		0.77
MPC		0.41
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.40
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-25665863;