rs3075570
Variant names:
Your query was ambiguous. Multiple possible variants found:
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-T
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA
- chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3
The NM_005219.5(DIAPH1):c.1833_1853delTCCTCCTCCTCCTCCTCCTCC(p.Pro612_Pro618del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000165 in 1,511,812 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000024 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
DIAPH1
NM_005219.5 disruptive_inframe_deletion
NM_005219.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.53
Publications
2 publications found
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]
DIAPH1 Gene-Disease associations (from GenCC):
- DIAPH1-related sensorineural hearing loss-thrombocytopenia syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- autosomal dominant nonsyndromic hearing loss 1Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
- progressive microcephaly-seizures-cortical blindness-developmental delay syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_005219.5
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DIAPH1 | ENST00000389054.8 | c.1833_1853delTCCTCCTCCTCCTCCTCCTCC | p.Pro612_Pro618del | disruptive_inframe_deletion | Exon 16 of 28 | 5 | NM_005219.5 | ENSP00000373706.4 | ||
| DIAPH1 | ENST00000518047.5 | c.1806_1826delTCCTCCTCCTCCTCCTCCTCC | p.Pro603_Pro609del | disruptive_inframe_deletion | Exon 15 of 27 | 5 | ENSP00000428268.2 | |||
| DIAPH1 | ENST00000647433.1 | c.1833_1853delTCCTCCTCCTCCTCCTCCTCC | p.Pro612_Pro618del | disruptive_inframe_deletion | Exon 16 of 29 | ENSP00000494675.1 | ||||
| DIAPH1 | ENST00000647330.1 | n.*1060_*1080delTCCTCCTCCTCCTCCTCCTCC | downstream_gene_variant | ENSP00000494308.1 |
Frequencies
GnomAD3 genomes 0.0000239 AC: 3AN: 125478Hom.: 0 Cov.: 28 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
125478
Hom.:
Cov.:
28
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000159 AC: 22AN: 1386334Hom.: 0 AF XY: 0.0000161 AC XY: 11AN XY: 683650 show subpopulations
GnomAD4 exome
AF:
AC:
22
AN:
1386334
Hom.:
AF XY:
AC XY:
11
AN XY:
683650
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31388
American (AMR)
AF:
AC:
1
AN:
35304
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24734
East Asian (EAS)
AF:
AC:
0
AN:
35360
South Asian (SAS)
AF:
AC:
0
AN:
77860
European-Finnish (FIN)
AF:
AC:
0
AN:
47518
Middle Eastern (MID)
AF:
AC:
0
AN:
4444
European-Non Finnish (NFE)
AF:
AC:
21
AN:
1072274
Other (OTH)
AF:
AC:
0
AN:
57452
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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10
<30
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Age
GnomAD4 genome 0.0000239 AC: 3AN: 125478Hom.: 0 Cov.: 28 AF XY: 0.0000166 AC XY: 1AN XY: 60152 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
125478
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
60152
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32940
American (AMR)
AF:
AC:
0
AN:
12422
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3078
East Asian (EAS)
AF:
AC:
0
AN:
4354
South Asian (SAS)
AF:
AC:
0
AN:
3778
European-Finnish (FIN)
AF:
AC:
0
AN:
7764
Middle Eastern (MID)
AF:
AC:
0
AN:
226
European-Non Finnish (NFE)
AF:
AC:
3
AN:
58434
Other (OTH)
AF:
AC:
0
AN:
1678
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.558
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Uncertain:1
-
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame deletion of 7 Proline amino acids at position 614 within a repetitive string of Prolines and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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