rs63751898

chr4-8871374-CCTCCCCGCCGGGCCCGGTGCCCGCGA-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_018942.3(HMX1):c.215_240del(p.Leu72ArgfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L72L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMX1 NM_018942.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.21

Genes affected

HMX1 (HGNC:5017): (H6 family homeobox 1) This gene encodes a transcription factor that belongs to the H6 family of homeobox proteins. This protein can bind a 5'-CAAG-3' core DNA sequence, and it is involved in the development of craniofacial structures. Mutations in this gene cause oculoauricular syndrome, a disorder of the eye and external ear. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP5: Variant 4-8871374-CCTCCCCGCCGGGCCCGGTGCCCGCGA-C is Pathogenic according to our data. Variant chr4-8871374-CCTCCCCGCCGGGCCCGGTGCCCGCGA-C is described in ClinVar as [Pathogenic]. Clinvar id is 14865.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMX1	NM_018942.3	c.215_240del	p.Leu72ArgfsTer51	frameshift_variant	1/2	ENST00000400677.5
HMX1	NM_001306142.2	c.215_240del	p.Leu72ArgfsTer51	frameshift_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMX1	ENST00000400677.5	c.215_240del	p.Leu72ArgfsTer51	frameshift_variant	1/2	1	NM_018942.3	P1
HMX1	ENST00000506970.2	c.215_240del	p.Leu72ArgfsTer51	frameshift_variant	1/2	1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Oculoauricular syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2008

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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: rs63751898; hg19: chr4-8873100;