rs200971068
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003924.4(PHOX2B):c.70T>C(p.Ser24Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000663 in 1,614,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S24W) has been classified as Uncertain significance.
Frequency
Consequence
NM_003924.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHOX2B | NM_003924.4 | c.70T>C | p.Ser24Pro | missense_variant | 1/3 | ENST00000226382.4 | |
PHOX2B-AS1 | XR_001741671.2 | n.193A>G | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHOX2B | ENST00000226382.4 | c.70T>C | p.Ser24Pro | missense_variant | 1/3 | 1 | NM_003924.4 | P1 | |
PHOX2B-AS1 | ENST00000508038.1 | n.249A>G | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000171 AC: 43AN: 250850Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135652
GnomAD4 exome AF: 0.0000684 AC: 100AN: 1461712Hom.: 1 Cov.: 31 AF XY: 0.0000949 AC XY: 69AN XY: 727162
GnomAD4 genome ? AF: 0.0000459 AC: 7AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74498
ClinVar
Submissions by phenotype
Haddad syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 11, 2024 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at