chr1-154489201-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001010846.3(SHE):c.874A>G(p.Thr292Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,668 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
SHE
NM_001010846.3 missense
NM_001010846.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 2.42
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2955942).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHE | NM_001010846.3 | c.874A>G | p.Thr292Ala | missense_variant | 3/6 | ENST00000304760.3 | |
SHE | XM_011509163.4 | c.874A>G | p.Thr292Ala | missense_variant | 3/7 | ||
SHE | XM_005244891.6 | c.874A>G | p.Thr292Ala | missense_variant | 3/6 | ||
SHE | NR_135169.2 | n.1260A>G | non_coding_transcript_exon_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHE | ENST00000304760.3 | c.874A>G | p.Thr292Ala | missense_variant | 3/6 | 1 | NM_001010846.3 | P1 | |
SHE | ENST00000555188.5 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000264 AC: 4AN: 151780Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251300Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135874
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727246
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GnomAD4 genome ? AF: 0.0000264 AC: 4AN: 151780Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74092
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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 | Oct 25, 2023 | The c.874A>G (p.T292A) alteration is located in exon 3 (coding exon 3) of the SHE gene. This alteration results from a A to G substitution at nucleotide position 874, causing the threonine (T) at amino acid position 292 to be replaced by an alanine (A). 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
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of phosphorylation at T292 (P = 0.0034);
MVP
MPC
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