NM_018942.3:c.*72G>T

Variant names:

• chr4-8867621-C-A
• rs182509379
• NM_018942.3:c.*72G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018942.3(HMX1):​c.*72G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000953 in 1,049,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: HMX1 NM_018942.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 0 publications found

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]

HMX1 Gene-Disease associations (from GenCC):

• oculoauricular syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018942.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMX1	NM_018942.3	MANE Select	c.*72G>T		3_prime_UTR	Exon 2 of 2	NP_061815.2	Q9NP08
	HMX1	NM_001306142.2		c.394+3600G>T		intron	N/A	NP_001293071.1	F1T0J4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMX1	ENST00000400677.5	TSL:1 MANE Select	c.*72G>T		3_prime_UTR	Exon 2 of 2	ENSP00000383516.3	Q9NP08
	HMX1	ENST00000506970.2	TSL:1	c.394+3600G>T		intron	N/A	ENSP00000446997.2	F1T0J4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.53e-7 AC: 1 AN: 1049760 Hom.: 0 Cov.: 37 AF XY: 0.00000202 AC XY: 1 AN XY: 495560

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21600

American (AMR) AF: 0.00 AC: 0 AN: 7408

Ashkenazi Jewish (ASJ) AF: 0.0000774 AC: 1 AN: 12926

East Asian (EAS) AF: 0.00 AC: 0 AN: 24030

South Asian (SAS) AF: 0.00 AC: 0 AN: 19120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2976

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 900320

Other (OTH) AF: 0.00 AC: 0 AN: 41296

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.69
PhyloP100		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs182509379; hg19: chr4-8869347;