NM_018942.3:c.*146C>T

Variant names:

• chr4-8867547-G-A
• rs146878642
• NM_018942.3:c.*146C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018942.3(HMX1):​c.*146C>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 0.00854 in 1,184,266 control chromosomes in the GnomAD database, including 561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (352 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (209 hom.)
• Consequence: HMX1 NM_018942.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.11
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-8867547-G-A is Benign according to our data. Variant chr4-8867547-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

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.*146C>T		3_prime_UTR	Exon 2 of 2	NP_061815.2	Q9NP08
	HMX1	NM_001306142.2		c.394+3674C>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.*146C>T		3_prime_UTR	Exon 2 of 2	ENSP00000383516.3	Q9NP08
	HMX1	ENST00000506970.2	TSL:1	c.394+3674C>T		intron	N/A	ENSP00000446997.2	F1T0J4

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5610 AN: 152058 Hom.: 352 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0136

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0291

GnomAD4 exome AF: 0.00435 AC: 4489 AN: 1032090 Hom.: 209 Cov.: 37 AF XY: 0.00424 AC XY: 2067 AN XY: 487048

African (AFR) AF: 0.130 AC: 2733 AN: 21052

American (AMR) AF: 0.0133 AC: 91 AN: 6850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12176

East Asian (EAS) AF: 0.00867 AC: 194 AN: 22370

South Asian (SAS) AF: 0.0374 AC: 685 AN: 18304

European-Finnish (FIN) AF: 0.0000526 AC: 1 AN: 19024

Middle Eastern (MID) AF: 0.0113 AC: 30 AN: 2658

European-Non Finnish (NFE) AF: 0.000254 AC: 226 AN: 889674

Other (OTH) AF: 0.0132 AC: 529 AN: 39982

GnomAD4 genome AF: 0.0370 AC: 5623 AN: 152176 Hom.: 352 Cov.: 33 AF XY: 0.0361 AC XY: 2684 AN XY: 74418

African (AFR) AF: 0.122 AC: 5056 AN: 41496

American (AMR) AF: 0.0137 AC: 210 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0136 AC: 70 AN: 5152

South Asian (SAS) AF: 0.0382 AC: 184 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 67998

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.0404

Asia WGS AF: 0.0310 AC: 109 AN: 3476

ClinVar

ClinVar submissions

Significance: 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	-0.79
CADD	Benign	2.5
DANN	Benign	0.91
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs146878642; hg19: chr4-8869273;