5-177385813-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_003052.5(SLC34A1):c.72G>T(p.Met24Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,613,344 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 (★★).
Frequency
Consequence
NM_003052.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC34A1 | NM_003052.5 | c.72G>T | p.Met24Ile | missense_variant | 2/13 | ENST00000324417.6 | NP_003043.3 | |
SLC34A1 | NM_001167579.2 | c.72G>T | p.Met24Ile | missense_variant | 2/9 | NP_001161051.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC34A1 | ENST00000324417.6 | c.72G>T | p.Met24Ile | missense_variant | 2/13 | 1 | NM_003052.5 | ENSP00000321424.4 | ||
SLC34A1 | ENST00000512593.5 | c.72G>T | p.Met24Ile | missense_variant | 2/9 | 2 | ENSP00000423022.1 | |||
SLC34A1 | ENST00000504577.5 | c.72G>T | p.Met24Ile | missense_variant | 2/4 | 4 | ENSP00000423733.1 | |||
SLC34A1 | ENST00000507685.5 | n.156G>T | non_coding_transcript_exon_variant | 2/10 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000486 AC: 12AN: 246910Hom.: 0 AF XY: 0.0000449 AC XY: 6AN XY: 133648
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461220Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 726860
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74300
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 21, 2024 | The c.72G>T (p.M24I) alteration is located in exon 2 (coding exon 1) of the SLC34A1 gene. This alteration results from a G to T substitution at nucleotide position 72, causing the methionine (M) at amino acid position 24 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hypophosphatemic nephrolithiasis/osteoporosis 1;C3150652:Fanconi renotubular syndrome 2;C4310473:Hypercalcemia, infantile, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 09, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 18, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SLC34A1-related conditions. This variant is present in population databases (rs146812061, ExAC 0.009%). This sequence change replaces methionine with isoleucine at codon 24 of the SLC34A1 protein (p.Met24Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at