Genetic Variant NM_005523.6:c.595G>C (chr7-27184550-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005523.6(HOXA11):c.595G>C(p.Gly199Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000813 in 1,229,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G199C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

HOXA11
NM_005523.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16506675).

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.595G>C	p.Gly199Arg	missense	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.595G>C	p.Gly199Arg	missense	Exon 1 of 2	ENSP00000006015.3	P31270
HOXA11	ENST00000517402.1	TSL:1	c.502G>C	p.Gly168Arg	missense	Exon 2 of 3	ENSP00000448962.1	H0YIA6
HOXA11-AS	ENST00000520360.6	TSL:5	n.44C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.13e-7

AC:

AN:

1229998

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

608186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25180

American (AMR)

AF:

0.00

AC:

AN:

26854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22292

East Asian (EAS)

AF:

0.0000344

AC:

AN:

29058

South Asian (SAS)

AF:

0.00

AC:

AN:

66220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3932

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

961706

Other (OTH)

AF:

0.00

AC:

AN:

51070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.22

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.60

M_CAP

Benign

0.025

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.55

PhyloP100

0.12

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.50

REVEL

Benign

0.25

Sift

Benign

0.48

Sift4G

Benign

0.20

Polyphen

0.62

Vest4

0.14

MutPred

0.33

Gain of methylation at G199 (P = 0.0237)

MVP

0.76

MPC

1.1

ClinPred

0.17

GERP RS

1.2

Varity_R

0.053

gMVP

0.50

Mutation Taster

=96/4

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over