10-100977729-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_017893.4(SEMA4G):āc.434T>Cā(p.Ile145Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_017893.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEMA4G | NM_017893.4 | c.434T>C | p.Ile145Thr | missense_variant, splice_region_variant | 5/15 | ENST00000210633.4 | NP_060363.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SEMA4G | ENST00000210633.4 | c.434T>C | p.Ile145Thr | missense_variant, splice_region_variant | 5/15 | 1 | NM_017893.4 | ENSP00000210633 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458934Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726062
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2023 | The c.434T>C (p.I145T) alteration is located in exon 4 (coding exon 4) of the SEMA4G gene. This alteration results from a T to C substitution at nucleotide position 434, causing the isoleucine (I) at amino acid position 145 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at