4-8867639-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018942.3(HMX1):​c.*54G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,212,636 control chromosomes in the GnomAD database, including 1,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 1064 hom., cov: 33)
Exomes 𝑓: 0.0069 ( 623 hom. )

Consequence

HMX1
NM_018942.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.46
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 4-8867639-C-T is Benign according to our data. Variant chr4-8867639-C-T is described in ClinVar as [Benign]. Clinvar id is 1271782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMX1NM_018942.3 linkc.*54G>A 3_prime_UTR_variant Exon 2 of 2 ENST00000400677.5 NP_061815.2 Q9NP08
HMX1NM_001306142.2 linkc.394+3582G>A intron_variant Intron 1 of 1 NP_001293071.1 Q9NP08F1T0J4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMX1ENST00000400677 linkc.*54G>A 3_prime_UTR_variant Exon 2 of 2 1 NM_018942.3 ENSP00000383516.3 Q9NP08
HMX1ENST00000506970.2 linkc.394+3582G>A intron_variant Intron 1 of 1 1 ENSP00000446997.2 F1T0J4

Frequencies

GnomAD3 genomes
AF:
0.0649
AC:
9866
AN:
152124
Hom.:
1061
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.220
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0220
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0135
Gnomad SAS
AF:
0.0397
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.000691
Gnomad OTH
AF:
0.0473
GnomAD4 exome
AF:
0.00689
AC:
7301
AN:
1060396
Hom.:
623
Cov.:
37
AF XY:
0.00665
AC XY:
3329
AN XY:
500636
show subpopulations
Gnomad4 AFR exome
AF:
0.229
Gnomad4 AMR exome
AF:
0.0221
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00839
Gnomad4 SAS exome
AF:
0.0374
Gnomad4 FIN exome
AF:
0.0000489
Gnomad4 NFE exome
AF:
0.000323
Gnomad4 OTH exome
AF:
0.0196
GnomAD4 genome
AF:
0.0649
AC:
9886
AN:
152240
Hom.:
1064
Cov.:
33
AF XY:
0.0626
AC XY:
4659
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.220
Gnomad4 AMR
AF:
0.0220
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0136
Gnomad4 SAS
AF:
0.0389
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000691
Gnomad4 OTH
AF:
0.0468
Alfa
AF:
0.0376
Hom.:
74
Bravo
AF:
0.0720
Asia WGS
AF:
0.0360
AC:
124
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 31, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.65
DANN
Benign
0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7293298; hg19: chr4-8869365; API