rs111033469
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BS1_Supporting
The NM_015404.4(WHRN):c.619G>T(p.Ala207Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000248 in 1,610,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015404.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WHRN | NM_015404.4 | c.619G>T | p.Ala207Ser | missense_variant, splice_region_variant | 2/12 | ENST00000362057.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WHRN | ENST00000362057.4 | c.619G>T | p.Ala207Ser | missense_variant, splice_region_variant | 2/12 | 1 | NM_015404.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000288 AC: 7AN: 243242Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 131976
GnomAD4 exome AF: 0.00000754 AC: 11AN: 1458158Hom.: 0 Cov.: 31 AF XY: 0.00000827 AC XY: 6AN XY: 725342
GnomAD4 genome ? AF: 0.000190 AC: 29AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74454
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 07, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Ala207Ser varia nt in DFNB31 has not been reported in the literature but has been identified by our laboratory in one Black individual with unilateral hearing loss and an enlar ged vestibular aqueduct, though it was not felt that this variant was causative. Computational analyses (biochemical amino acid properties, conservation, AlignG VGD, PolyPhen2, and SIFT) suggest that the Ala207Ser variant may not impact the protein, though this information is not predictive enough to rule out pathogenic ity. In summary, the clinical significance of this variant cannot be determined with certainty; however based upon the computational predictions, we would lean towards a more likely benign role. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.619G>T (p.A207S) alteration is located in exon 2 (coding exon 2) of the WHRN gene. This alteration results from a G to T substitution at nucleotide position 619, causing the alanine (A) at amino acid position 207 to be replaced by a serine (S). 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