chr15-45172277-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001394037.1(SHF):c.1030C>T(p.Arg344Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,611,954 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
SHF
NM_001394037.1 missense
NM_001394037.1 missense
Scores
1
6
9
Clinical Significance
Conservation
PhyloP100: 0.601
Genes affected
SHF (HGNC:25116): (Src homology 2 domain containing F) Predicted to enable phosphotyrosine residue binding activity. Predicted to be involved in apoptotic process. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24003762).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHF | NM_001394037.1 | c.1030C>T | p.Arg344Trp | missense_variant | 5/7 | ENST00000690270.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHF | ENST00000690270.1 | c.1030C>T | p.Arg344Trp | missense_variant | 5/7 | NM_001394037.1 | P1 | ||
ENST00000560034.1 | n.191+1743G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 247912Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133984
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1459716Hom.: 0 Cov.: 31 AF XY: 0.0000262 AC XY: 19AN XY: 726088
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74434
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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 | Aug 02, 2021 | The c.835C>T (p.R279W) alteration is located in exon 6 (coding exon 5) of the SHF gene. This alteration results from a C to T substitution at nucleotide position 835, causing the arginine (R) at amino acid position 279 to be replaced by a tryptophan (W). 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
Uncertain
Dann
Pathogenic
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.44
.;B;.;.
Vest4
MVP
MPC
0.96
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at