chr5-141584136-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005219.5(DIAPH1):c.390C>T(p.Tyr130Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,607,476 control chromosomes in the GnomAD database, including 555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_005219.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.390C>T | p.Tyr130Tyr | synonymous_variant | Exon 4 of 28 | 5 | NM_005219.5 | ENSP00000373706.4 | ||
DIAPH1 | ENST00000518047.5 | c.363C>T | p.Tyr121Tyr | synonymous_variant | Exon 3 of 27 | 5 | ENSP00000428268.2 | |||
DIAPH1 | ENST00000647433.1 | c.390C>T | p.Tyr130Tyr | synonymous_variant | Exon 4 of 29 | ENSP00000494675.1 | ||||
DIAPH1 | ENST00000523100.5 | n.390C>T | non_coding_transcript_exon_variant | Exon 4 of 11 | 5 | ENSP00000428208.1 |
Frequencies
GnomAD3 genomes AF: 0.0343 AC: 5210AN: 151994Hom.: 276 Cov.: 32
GnomAD3 exomes AF: 0.00908 AC: 2258AN: 248734Hom.: 125 AF XY: 0.00645 AC XY: 870AN XY: 134888
GnomAD4 exome AF: 0.00348 AC: 5062AN: 1455378Hom.: 281 Cov.: 30 AF XY: 0.00290 AC XY: 2101AN XY: 724412
GnomAD4 genome AF: 0.0343 AC: 5219AN: 152098Hom.: 274 Cov.: 32 AF XY: 0.0328 AC XY: 2440AN XY: 74350
ClinVar
Submissions by phenotype
not specified Benign:3
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Tyr130Tyr in Exon 04 of DIAPH1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 11.9% (376/3154) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs34296458). -
Autosomal dominant nonsyndromic hearing loss 1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
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Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at