7-27173570-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_018951.4(HOXA10):c.737C>T(p.Pro246Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000954 in 1,467,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P246P) has been classified as Benign.
Frequency
Consequence
NM_018951.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOXA10 | NM_018951.4 | c.737C>T | p.Pro246Leu | missense_variant | 1/2 | ENST00000283921.5 | |
HOXA10-HOXA9 | NR_037940.1 | n.616+6076C>T | intron_variant, non_coding_transcript_variant | ||||
HOXA10 | NR_037939.2 | n.217-1397C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOXA10 | ENST00000283921.5 | c.737C>T | p.Pro246Leu | missense_variant | 1/2 | 1 | NM_018951.4 | P2 | |
HOXA10 | ENST00000396344.4 | c.11-1397C>T | intron_variant | 1 | A1 | ||||
HOXA9 | ENST00000465941.1 | n.479+1132C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152066Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000304 AC: 4AN: 1315162Hom.: 0 Cov.: 33 AF XY: 0.00000309 AC XY: 2AN XY: 647178
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152066Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74288
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 06, 2023 | The c.737C>T (p.P246L) alteration is located in exon 1 (coding exon 1) of the HOXA10 gene. This alteration results from a C to T substitution at nucleotide position 737, causing the proline (P) at amino acid position 246 to be replaced by a leucine (L). 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