NM_018942.3:c.*72G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_018942.3(HMX1):​c.*72G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,201,994 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (8 hom., cov: 33)
  • Exomes 𝑓: 0.012 (85 hom.)
• Consequence: HMX1 NM_018942.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.129
• Publications: 1 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-8867621-C-G is Benign according to our data. Variant chr4-8867621-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1206465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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>C		3_prime_UTR	Exon 2 of 2	NP_061815.2	Q9NP08
	HMX1	NM_001306142.2		c.394+3600G>C		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>C		3_prime_UTR	Exon 2 of 2	ENSP00000383516.3	Q9NP08
	HMX1	ENST00000506970.2	TSL:1	c.394+3600G>C		intron	N/A	ENSP00000446997.2	F1T0J4

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 1165 AN: 152144 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00773

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.0118 AC: 12356 AN: 1049734 Hom.: 85 Cov.: 37 AF XY: 0.0118 AC XY: 5861 AN XY: 495548

African (AFR) AF: 0.00153 AC: 33 AN: 21600

American (AMR) AF: 0.00864 AC: 64 AN: 7408

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 275 AN: 12926

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

South Asian (SAS) AF: 0.00424 AC: 81 AN: 19120

European-Finnish (FIN) AF: 0.00478 AC: 96 AN: 20082

Middle Eastern (MID) AF: 0.00470 AC: 14 AN: 2976

European-Non Finnish (NFE) AF: 0.0126 AC: 11368 AN: 900300

Other (OTH) AF: 0.0103 AC: 425 AN: 41292

GnomAD4 genome AF: 0.00765 AC: 1165 AN: 152260 Hom.: 8 Cov.: 33 AF XY: 0.00712 AC XY: 530 AN XY: 74438

African (AFR) AF: 0.00173 AC: 72 AN: 41576

American (AMR) AF: 0.00772 AC: 118 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3470

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5148

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4826

European-Finnish (FIN) AF: 0.00442 AC: 47 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 816 AN: 68006

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.00864 Hom.: 1

Bravo AF: 0.00774

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.46
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

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;