dbSNP rs1165767194: HOXA11:p.Glu202* (chr7-27184541-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005523.6(HOXA11):c.604G>T(p.Glu202*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000742 in 1,348,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

HOXA11
NM_005523.6 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.79

Publications

0 publications found

Variant links:

Genes affected

HOXA11 (HGNC:5101): (homeobox A11) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. This gene is involved in the regulation of uterine development and is required for female fertility. Mutations in this gene can cause radio-ulnar synostosis with amegakaryocytic thrombocytopenia. [provided by RefSeq, Jul 2008]

HOXA11 links:

HOXA11-AS (HGNC:24957): (HOXA11 antisense RNA) This gene produces a long non-coding RNA in antisense to transcription of the homeobox A11 gene. This transcript may associate with chromatin factors such as Polycomb repressive complex and act as a sponge for microRNAs, thereby participating in the regulation of expression of target genes. High levels of this transcript may be associated with tumor progression. [provided by RefSeq, Dec 2017]

HOXA11-AS links:

ENSG00000293630 (HGNC:):

ENSG00000293630 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005523.6. 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
	HOXA11	NM_005523.6	MANE Select	c.604G>T	p.Glu202*	stop_gained	Exon 1 of 2	NP_005514.1	P31270

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA11	ENST00000006015.4	TSL:1 MANE Select	c.604G>T	p.Glu202*	stop_gained	Exon 1 of 2	ENSP00000006015.3	P31270
HOXA11	ENST00000517402.1	TSL:1	c.511G>T	p.Glu171*	stop_gained	Exon 2 of 3	ENSP00000448962.1	H0YIA6
HOXA11-AS	ENST00000520360.6	TSL:5	n.35C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.42e-7

AC:

AN:

1348002

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

664748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27620

American (AMR)

AF:

0.00

AC:

AN:

30436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23862

East Asian (EAS)

AF:

0.00

AC:

AN:

30598

South Asian (SAS)

AF:

0.00

AC:

AN:

74410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4250

European-Non Finnish (NFE)

AF:

9.49e-7

AC:

AN:

1054184

Other (OTH)

AF:

0.00

AC:

AN:

55566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.60

BayesDel_noAF

Pathogenic

0.50

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.40

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.97

PhyloP100

2.8

Vest4

0.61

GERP RS

3.7

Mutation Taster

=8/192

disease causing (fs/PTC)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over