rs1376643176

Variant names:

• chr4-8867694-C-A
• NM_018942.3:c.1046G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-8867694-C-A
• chr4-8867694-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_018942.3(HMX1):​c.1046G>T​(p.Ter349Leuext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000906 in 1,103,276 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. Synonymous variant affecting the same amino acid position (i.e. *349*) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: HMX1 NM_018942.3 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_018942.3 Downstream stopcodon found after 423 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMX1	NM_018942.3	c.1046G>T	p.Ter349Leuext*?	stop_lost	Exon 2 of 2	ENST00000400677.5	NP_061815.2
HMX1	NM_001306142.2	c.394+3527G>T		intron_variant	Intron 1 of 1		NP_001293071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMX1	ENST00000400677.5	c.1046G>T	p.Ter349Leuext*?	stop_lost	Exon 2 of 2	1	NM_018942.3	ENSP00000383516.3
HMX1	ENST00000506970.2	c.394+3527G>T		intron_variant	Intron 1 of 1	1		ENSP00000446997.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.06e-7 AC: 1 AN: 1103276 Hom.: 0 Cov.: 37 AF XY: 0.00000190 AC XY: 1 AN XY: 526354

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.91
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
Vest4		0.091
GERP RS		3.9

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-8869420;