4-41745984-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003924.4(PHOX2B):āc.768A>Gā(p.Ala256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000295 in 1,255,478 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. A256A) has been classified as Likely benign.
Frequency
Consequence
NM_003924.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHOX2B | NM_003924.4 | c.768A>G | p.Ala256= | synonymous_variant | 3/3 | ENST00000226382.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHOX2B | ENST00000226382.4 | c.768A>G | p.Ala256= | synonymous_variant | 3/3 | 1 | NM_003924.4 | P1 | |
PHOX2B | ENST00000510424.2 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000137 AC: 2AN: 146472Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000563 AC: 20AN: 35526Hom.: 1 AF XY: 0.000555 AC XY: 12AN XY: 21632
GnomAD4 exome AF: 0.0000316 AC: 35AN: 1108904Hom.: 1 Cov.: 31 AF XY: 0.0000243 AC XY: 13AN XY: 533984
GnomAD4 genome AF: 0.0000136 AC: 2AN: 146574Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 1AN XY: 71328
ClinVar
Submissions by phenotype
Haddad syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 30, 2022 | This alteration is classified as likely 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