7-27184501-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005523.6(HOXA11):​c.644G>T​(p.Arg215Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000114 in 1,533,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

HOXA11
NM_005523.6 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.39887866).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HOXA11NM_005523.6 linkuse as main transcriptc.644G>T p.Arg215Leu missense_variant 1/2 ENST00000006015.4 NP_005514.1 P31270

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HOXA11ENST00000006015.4 linkuse as main transcriptc.644G>T p.Arg215Leu missense_variant 1/21 NM_005523.6 ENSP00000006015.3 P31270
HOXA11ENST00000517402.1 linkuse as main transcriptc.551G>T p.Arg184Leu missense_variant 2/31 ENSP00000448962.1 H0YIA6
HOXA11-ASENST00000520360.6 linkuse as main transcriptn.-6C>A upstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
151788
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000726
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000300
AC:
4
AN:
133172
Hom.:
0
AF XY:
0.0000138
AC XY:
1
AN XY:
72552
show subpopulations
Gnomad AFR exome
AF:
0.000209
Gnomad AMR exome
AF:
0.000132
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000123
AC:
170
AN:
1381486
Hom.:
0
Cov.:
31
AF XY:
0.000107
AC XY:
73
AN XY:
681768
show subpopulations
Gnomad4 AFR exome
AF:
0.0000336
Gnomad4 AMR exome
AF:
0.0000579
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000209
Gnomad4 NFE exome
AF:
0.000150
Gnomad4 OTH exome
AF:
0.0000875
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
151788
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74072
show subpopulations
Gnomad4 AFR
AF:
0.0000726
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000582
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.0000105
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingMayo Clinic Laboratories, Mayo ClinicJun 19, 2024PM1_supporting -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
23
DANN
Benign
0.92
DEOGEN2
Benign
0.36
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.55
T
M_CAP
Pathogenic
0.95
D
MetaRNN
Benign
0.40
T
MetaSVM
Uncertain
-0.055
T
MutationAssessor
Benign
1.0
L
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.36
Sift
Benign
0.26
T
Sift4G
Benign
0.29
T
Polyphen
0.49
P
Vest4
0.38
MVP
0.78
MPC
1.2
ClinPred
0.049
T
GERP RS
3.7
Varity_R
0.23
gMVP
0.61

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: rs764993725; hg19: chr7-27224120; API