Genetic Variant HOXA9:p.Lys209Lys (chr7-27163795-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_152739.4(HOXA9):c.627G>A(p.Lys209Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,613,988 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 121 hom. )

Consequence

HOXA9
NM_152739.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.31

Publications

0 publications found

Variant links:

Genes affected

HOXA9 (HGNC:5109): (homeobox A9) 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 highly similar to the abdominal-B (Abd-B) gene of Drosophila. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis. Read-through transcription exists between this gene and the upstream homeobox A10 (HOXA10) gene.[provided by RefSeq, Mar 2011]

HOXA9 links:

HOXA10-HOXA9 (HGNC:51908):

HOXA10-HOXA9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 7-27163795-C-T is Benign according to our data. Variant chr7-27163795-C-T is described in ClinVar as Benign. ClinVar VariationId is 787701.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.31 with no splicing effect.

BS2

High AC in GnomAd4 at 944 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152739.4. 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
	HOXA9	NM_152739.4	MANE Select	c.627G>A	p.Lys209Lys	synonymous	Exon 2 of 2	NP_689952.1	P31269
	HOXA10-HOXA9	NM_001433944.1		c.147G>A	p.Lys49Lys	synonymous	Exon 3 of 3	NP_001420873.1	D6RAR5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA9	ENST00000343483.7	TSL:1 MANE Select	c.627G>A	p.Lys209Lys	synonymous	Exon 2 of 2	ENSP00000343619.6	P31269
HOXA10-HOXA9	ENST00000470747.5	TSL:3	c.147G>A	p.Lys49Lys	synonymous	Exon 3 of 3	ENSP00000421799.3
HOXA9	ENST00000465941.1	TSL:1	n.526G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00622

AC:

945

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.0677

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00859

AC:

2161

AN:

251454

AF XY:

0.00879

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0682

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00651

GnomAD4 exome

AF:

0.00415

AC:

6061

AN:

1461868

Hom.:

121

Cov.:

AF XY:

0.00429

AC XY:

3118

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33480

American (AMR)

AF:

0.000827

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00505

AC:

132

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00871

AC:

751

AN:

86258

European-Finnish (FIN)

AF:

0.0635

AC:

3391

AN:

53410

Middle Eastern (MID)

AF:

0.00416

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00131

AC:

1453

AN:

1112000

Other (OTH)

AF:

0.00442

AC:

267

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

332

664

996

1328

1660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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

AF:

0.00621

AC:

944

AN:

152120

Hom.:

Cov.:

AF XY:

0.00896

AC XY:

666

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41502

American (AMR)

AF:

0.000327

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.0105

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.0677

AC:

717

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00213

AC:

145

AN:

68010

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

135

180

225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00233

Hom.:

Bravo

AF:

0.00110

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.6

(source)

DANN

Benign

0.89

PhyloP100

1.3

Mutation Taster

=94/6

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over