8-144099086-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_030974.4(SHARPIN):c.1042C>T(p.Leu348Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000705 in 1,418,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_030974.4 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 |
---|---|---|---|---|---|---|---|---|
SHARPIN | NM_030974.4 | c.1042C>T | p.Leu348Phe | missense_variant | 7/9 | ENST00000398712.7 | NP_112236.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SHARPIN | ENST00000398712.7 | c.1042C>T | p.Leu348Phe | missense_variant | 7/9 | 1 | NM_030974.4 | ENSP00000381698 | P1 | |
SHARPIN | ENST00000359551.6 | c.923-92C>T | intron_variant, NMD_transcript_variant | 1 | ENSP00000352551 | |||||
SHARPIN | ENST00000532536.5 | c.166C>T | p.Leu56Phe | missense_variant | 2/3 | 3 | ENSP00000432355 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000705 AC: 10AN: 1418094Hom.: 0 Cov.: 28 AF XY: 0.00000567 AC XY: 4AN XY: 705272
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The c.1042C>T (p.L348F) alteration is located in exon 7 (coding exon 7) of the SHARPIN gene. This alteration results from a C to T substitution at nucleotide position 1042, causing the leucine (L) at amino acid position 348 to be replaced by a phenylalanine (F). 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