rs193920767

chr5-177385754-G-A

Variant summary

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

The NM_003052.5(SLC34A1):c.13G>A(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SLC34A1 NM_003052.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.578

Genes affected

SLC34A1 (HGNC:11019): (solute carrier family 34 member 1) Enables sodium:phosphate symporter activity. Involved in several processes, including phosphate ion homeostasis; phosphate ion transport; and response to lead ion. Located in several cellular components, including apical plasma membrane; mitotic spindle; and nuclear speck. Implicated in several diseases, including Fanconi syndrome (multiple); chronic kidney disease; hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; and nephrolithiasis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062136263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A1	NM_003052.5	c.13G>A	p.Gly5Arg	missense_variant	2/13	ENST00000324417.6
SLC34A1	NM_001167579.2	c.13G>A	p.Gly5Arg	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A1	ENST00000324417.6	c.13G>A	p.Gly5Arg	missense_variant	2/13	1	NM_003052.5	P1
SLC34A1	ENST00000512593.5	c.13G>A	p.Gly5Arg	missense_variant	2/9	2
SLC34A1	ENST00000504577.5	c.13G>A	p.Gly5Arg	missense_variant	2/4	4
SLC34A1	ENST00000507685.5	n.97G>A		non_coding_transcript_exon_variant	2/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000812 AC: 2 AN: 246234 Hom.: 0 AF XY: 0.00000751 AC XY: 1 AN XY: 133118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000663

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460612 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6 AN XY: 726496

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000815

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	15
Dann	Benign	0.67
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.43	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0080	.;.;B
Vest4		0.31, 0.30
MutPred		0.15		Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);
MVP		0.33
MPC		0.080
ClinPred		0.037	T
GERP RS		1.6
Varity_R		0.045
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs193920767; hg19: chr5-176812755; COSMIC: COSV60998982; COSMIC: COSV60998982;