15-45198773-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000568314.1(ENSG00000259932):n.367C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,607,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Scores
3
16
Splicing: ADA: 0.0002256
2
Clinical Significance
Conservation
PhyloP100: 1.06
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04458937).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHF | NM_138356.3 | c.302C>T | p.Pro101Leu | missense_variant, splice_region_variant | 2/8 | ||
SHF | NM_001394041.1 | c.302C>T | p.Pro101Leu | missense_variant, splice_region_variant | 2/8 | ||
SHF | NM_001394043.1 | c.302C>T | p.Pro101Leu | missense_variant, splice_region_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENST00000568314.1 | n.367C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
ENST00000560034.1 | n.192-1085G>A | intron_variant, non_coding_transcript_variant | 5 | ||||||
SHF | ENST00000290894.12 | c.302C>T | p.Pro101Leu | missense_variant, splice_region_variant | 2/8 | 2 | |||
SHF | ENST00000561278.1 | c.-109+1954C>T | intron_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152204Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000525 AC: 13AN: 247686Hom.: 0 AF XY: 0.0000670 AC XY: 9AN XY: 134390
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1455726Hom.: 0 Cov.: 30 AF XY: 0.0000166 AC XY: 12AN XY: 723122
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GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74352
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ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.302C>T (p.P101L) alteration is located in exon 2 (coding exon 1) of the SHF gene. This alteration results from a C to T substitution at nucleotide position 302, causing the proline (P) at amino acid position 101 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at