rs1064797096

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5

The NM_005219.5(DIAPH1):​c.3624_3625delAG​(p.Ala1210fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

DIAPH1
NM_005219.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.20
Variant links:
Genes affected
DIAPH1 (HGNC:2876): (diaphanous related formin 1) This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0511 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-141524178-CCT-C is Pathogenic according to our data. Variant chr5-141524178-CCT-C is described in ClinVar as [Pathogenic]. Clinvar id is 424874.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-141524178-CCT-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DIAPH1NM_005219.5 linkuse as main transcriptc.3624_3625delAG p.Ala1210fs frameshift_variant 27/28 ENST00000389054.8 NP_005210.3 O60610-1Q6URC4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DIAPH1ENST00000389054.8 linkuse as main transcriptc.3624_3625delAG p.Ala1210fs frameshift_variant 27/285 NM_005219.5 ENSP00000373706.4 O60610-1
DIAPH1ENST00000518047.5 linkuse as main transcriptc.3597_3598delAG p.Ala1201fs frameshift_variant 26/275 ENSP00000428268.2 O60610-3
DIAPH1ENST00000647433.1 linkuse as main transcriptc.3624_3625delAG p.Ala1210fs frameshift_variant 27/29 ENSP00000494675.1 A0A2R8Y5N1
DIAPH1ENST00000468119.3 linkuse as main transcriptc.30_31delAG p.Ala12fs frameshift_variant 2/34 ENSP00000493546.1 H7C2W8

Frequencies

GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJul 20, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1064797096; hg19: chr5-140903745; API