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_240delTCGCGGGCACCGGGCCCGGCGGGGAG​(p.Leu72fs) 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).

• 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	Protein	UniProt
HMX1	NM_018942.3	c.215_240delTCGCGGGCACCGGGCCCGGCGGGGAG	p.Leu72fs	frameshift_variant	1/2	ENST00000400677.5	NP_061815.2
HMX1	NM_001306142.2	c.215_240delTCGCGGGCACCGGGCCCGGCGGGGAG	p.Leu72fs	frameshift_variant	1/2		NP_001293071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMX1	ENST00000400677.5	c.215_240delTCGCGGGCACCGGGCCCGGCGGGGAG	p.Leu72fs	frameshift_variant	1/2	1	NM_018942.3	ENSP00000383516.3
HMX1	ENST00000506970.2	c.215_240delTCGCGGGCACCGGGCCCGGCGGGGAG	p.Leu72fs	frameshift_variant	1/2	1		ENSP00000446997.2

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;