chr15-48843525-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_203349.4(SHC4):c.1367G>A(p.Arg456Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_203349.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SHC4 | NM_203349.4 | c.1367G>A | p.Arg456Gln | missense_variant | Exon 10 of 12 | ENST00000332408.9 | NP_976224.3 | |
SHC4 | XM_005254375.4 | c.818G>A | p.Arg273Gln | missense_variant | Exon 10 of 12 | XP_005254432.1 | ||
SHC4 | XM_047432492.1 | c.509G>A | p.Arg170Gln | missense_variant | Exon 7 of 9 | XP_047288448.1 | ||
SHC4 | XM_047432493.1 | c.509G>A | p.Arg170Gln | missense_variant | Exon 8 of 10 | XP_047288449.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251228Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135758
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727226
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1367G>A (p.R456Q) alteration is located in exon 10 (coding exon 10) of the SHC4 gene. This alteration results from a G to A substitution at nucleotide position 1367, causing the arginine (R) at amino acid position 456 to be replaced by a glutamine (Q). 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