chr12-53328228-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001173467.3(SP7):c.1214C>T(p.Thr405Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001173467.3 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 |
---|---|---|---|---|---|---|---|---|
SP7 | NM_001173467.3 | c.1214C>T | p.Thr405Met | missense_variant | 3/3 | ENST00000536324.4 | NP_001166938.1 | |
SP7 | NM_152860.2 | c.1214C>T | p.Thr405Met | missense_variant | 2/2 | NP_690599.1 | ||
SP7 | NM_001300837.2 | c.1160C>T | p.Thr387Met | missense_variant | 3/3 | NP_001287766.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SP7 | ENST00000536324.4 | c.1214C>T | p.Thr405Met | missense_variant | 3/3 | 2 | NM_001173467.3 | ENSP00000443827 | P1 | |
SP7 | ENST00000303846.3 | c.1214C>T | p.Thr405Met | missense_variant | 2/2 | 1 | ENSP00000302812 | P1 | ||
SP7 | ENST00000537210.2 | c.1160C>T | p.Thr387Met | missense_variant | 2/2 | 1 | ENSP00000441367 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000488 AC: 12AN: 245828Hom.: 0 AF XY: 0.0000598 AC XY: 8AN XY: 133742
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1460846Hom.: 0 Cov.: 29 AF XY: 0.0000427 AC XY: 31AN XY: 726700
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74458
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 19, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 405 of the SP7 protein (p.Thr405Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SP7-related conditions. ClinVar contains an entry for this variant (Variation ID: 1463854). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at