4-143693146-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001168235.2(FREM3):c.5242A>G(p.Lys1748Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000591 in 1,522,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001168235.2 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 | UniProt |
---|---|---|---|---|---|---|---|
FREM3 | NM_001168235.2 | c.5242A>G | p.Lys1748Glu | missense_variant | 2/8 | ENST00000329798.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FREM3 | ENST00000329798.5 | c.5242A>G | p.Lys1748Glu | missense_variant | 2/8 | 5 | NM_001168235.2 | P1 | |
GUSBP5 | ENST00000641328.1 | n.862-45829T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000438 AC: 6AN: 1370124Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 676002
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 06, 2023 | The c.5242A>G (p.K1748E) alteration is located in exon 2 (coding exon 2) of the FREM3 gene. This alteration results from a A to G substitution at nucleotide position 5242, causing the lysine (K) at amino acid position 1748 to be replaced by a glutamic acid (E). 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