rs3075570

Variant names:

• chr5-141573996-TGGAGGAGGAGGAGGAGGAGGA-T
• rs3075570
• NM_005219.5:c.1833_1853delTCCTCCTCCTCCTCCTCCTCC

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. Variant got -4 ACMG points: 0P and 4B. BS2

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. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5	c.1833_1853delTCCTCCTCCTCCTCCTCCTCC	p.Pro612_Pro618del	disruptive_inframe_deletion	Exon 16 of 28	ENST00000389054.8	NP_005210.3

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 AF: 0.0000239 AC: 3 AN: 125478 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000513

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000159 AC: 22 AN: 1386334 Hom.: 0 AF XY: 0.0000161 AC XY: 11 AN XY: 683650

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000283

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000196

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000239 AC: 3 AN: 125478 Hom.: 0 Cov.: 28 AF XY: 0.0000166 AC XY: 1 AN XY: 60152

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000513

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3075570; hg19: chr5-140953563;