rs63751898

Positions:

• chr4-8871374-CCTCCCCGCCGGGCCCGGTGCCCGCGA-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_018942.3(HMX1):​c.215_240del​(p.Leu72ArgfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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

- -

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;