rs570049997
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001038603.3(MARVELD2):c.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,553,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
MARVELD2
NM_001038603.3 3_prime_UTR
NM_001038603.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.171
Genes affected
MARVELD2 (HGNC:26401): (MARVEL domain containing 2) The protein encoded by this gene is a membrane protein found at the tight junctions between epithelial cells. The encoded protein helps establish epithelial barriers such as those in the organ of Corti, where these barriers are required for normal hearing. Defects in this gene are a cause of deafness autosomal recessive type 49 (DFNB49). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARVELD2 | NM_001038603.3 | c.*1C>T | 3_prime_UTR_variant | 7/7 | ENST00000325631.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARVELD2 | ENST00000325631.10 | c.*1C>T | 3_prime_UTR_variant | 7/7 | 1 | NM_001038603.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152030Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000563 AC: 14AN: 248608Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134846
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GnomAD4 exome AF: 0.0000178 AC: 25AN: 1401340Hom.: 0 Cov.: 26 AF XY: 0.0000214 AC XY: 15AN XY: 700188
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74392
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 26, 2016 | The c.*1C>T variant in MARVELD2 has not been previously reported in ndividuals w ith hearing loss. This variant has been identified in 8/118894 of the total chro mosomes from several populations by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs570049997). Although this variant has been seen in the general population, its frequency is not high enough to rule out a p athogenic role. This variant is in the 3' untranslated region (UTR). The nucle otide at this position is not conserved through species; however, this informati on does not provide strong support for or against an impact to the protein. In s ummary, the clinical significance of the c.*1C>T variant is uncertain. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at