12-71615275-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_144982.5(ZFC3H1):c.5186G>A(p.Arg1729His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,612,636 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1729C) has been classified as Uncertain significance.
Frequency
Consequence
NM_144982.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZFC3H1 | ENST00000378743.9 | c.5186G>A | p.Arg1729His | missense_variant | Exon 28 of 35 | 1 | NM_144982.5 | ENSP00000368017.4 | ||
ZFC3H1 | ENST00000552994.5 | n.5186G>A | non_coding_transcript_exon_variant | Exon 28 of 34 | 1 | ENSP00000446995.1 | ||||
ZFC3H1 | ENST00000546771.1 | n.177G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 3 | |||||
ZFC3H1 | ENST00000546475.1 | n.-127G>A | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000264 AC: 4AN: 151658Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248364Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134666
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1460978Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726750
GnomAD4 genome AF: 0.0000264 AC: 4AN: 151658Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 73992
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.5186G>A (p.R1729H) alteration is located in exon 28 (coding exon 28) of the ZFC3H1 gene. This alteration results from a G to A substitution at nucleotide position 5186, causing the arginine (R) at amino acid position 1729 to be replaced by a histidine (H). 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