chr10-113589082-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The ENST00000369358.8(NRAP):c.5089C>T(p.Gln1697Ter) variant causes a stop gained, splice region change. The variant allele was found at a frequency of 0.00000806 in 1,612,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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 (★).
Frequency
Consequence
ENST00000369358.8 stop_gained, 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 | UniProt |
---|---|---|---|---|---|---|---|
HABP2 | NM_004132.5 | c.*713G>A | 3_prime_UTR_variant | 13/13 | ENST00000351270.4 | ||
NRAP | NM_198060.4 | c.5089-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000359988.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HABP2 | ENST00000351270.4 | c.*713G>A | 3_prime_UTR_variant | 13/13 | 1 | NM_004132.5 | P1 | ||
NRAP | ENST00000359988.4 | c.5089-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_198060.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151934Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250566Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135424
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1460792Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726760
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151934Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74188
ClinVar
Submissions by phenotype
NRAP-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 17, 2023 | The NRAP c.5089C>T variant is predicted to result in premature protein termination (p.Gln1697*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-115348841-G-A). This variant is in the terminal exon, and no other variants have been reported as causative nearby or downstream. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at