rs397517940
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_194248.3(OTOF):āc.2972A>Gā(p.Asn991Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,609,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.2972A>G | p.Asn991Ser | missense_variant | 24/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.731A>G | p.Asn244Ser | missense_variant | 7/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.2972A>G | p.Asn991Ser | missense_variant | 24/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.731A>G | p.Asn244Ser | missense_variant | 7/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151992Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000492 AC: 12AN: 243862Hom.: 0 AF XY: 0.0000378 AC XY: 5AN XY: 132404
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1457800Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 724894
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151992Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2023 | The c.2972A>G (p.N991S) alteration is located in exon 24 (coding exon 24) of the OTOF gene. This alteration results from a A to G substitution at nucleotide position 2972, causing the asparagine (N) at amino acid position 991 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 07, 2011 | Asn991Ser in exon 24 of OTOF: This variant is not expected to have clinical sign ificance because computational analyses (PolyPhen, SIFT, AlignGVGD) do not sugge st a high likelihood of clinical significance primarily based upon a lack of con servation across species including mammals. Of note, chicken has a serine at thi s position despite high nearby amino acid conservation. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at