rs727503158
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001038603.3(MARVELD2):c.1059A>G(p.Ile353Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,613,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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_001038603.3 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 |
---|---|---|---|---|---|---|---|
MARVELD2 | NM_001038603.3 | c.1059A>G | p.Ile353Met | missense_variant | 2/7 | ENST00000325631.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARVELD2 | ENST00000325631.10 | c.1059A>G | p.Ile353Met | missense_variant | 2/7 | 1 | NM_001038603.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251128Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135768
GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461520Hom.: 0 Cov.: 35 AF XY: 0.0000481 AC XY: 35AN XY: 727100
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
Nonsyndromic Hearing Loss, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 28, 2013 | Ile353Met in exon 2 of MARVELD2: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, horse, pika, and tarsier have a methionine (Met) at this position despite high nearby amino acid conservation. In addition, computational analyses (PolyPh en2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at