7-27165166-C-T

Variant names:

• chr7-27165166-C-T
• rs763826633
• NM_152739.4:c.292G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152739.4(HOXA9):​c.292G>A​(p.Val98Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V98L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HOXA9 NM_152739.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501
• Publications: 0 publications found

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]

HOXA10-HOXA9 (HGNC:51908):

ACMG classification

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=0.17210189).

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.292G>A	p.Val98Met	missense	Exon 1 of 2	NP_689952.1	P31269
	HOXA10-HOXA9	NM_001433944.1		c.11-199G>A		intron	N/A	NP_001420873.1	D6RAR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA9	ENST00000343483.7	TSL:1 MANE Select	c.292G>A	p.Val98Met	missense	Exon 1 of 2	ENSP00000343619.6	P31269
	HOXA10-HOXA9	ENST00000470747.5	TSL:3	c.11-199G>A		intron	N/A	ENSP00000421799.3
	HOXA9	ENST00000465941.1	TSL:1	n.480-1325G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444836 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717316

African (AFR) AF: 0.00 AC: 0 AN: 32914

American (AMR) AF: 0.00 AC: 0 AN: 42668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.00 AC: 0 AN: 84752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103602

Other (OTH) AF: 0.00 AC: 0 AN: 59434

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.50
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.22
Sift	Benign	0.23	T
Sift4G	Benign	0.17	T
Polyphen		0.11	B
Vest4		0.25
MutPred		0.49		Gain of disorder (P = 0.053)
MVP		0.86
MPC		0.44
ClinPred		0.26	T
GERP RS		2.4
PromoterAI		0.15	Neutral
Varity_R		0.043
gMVP		0.18
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs763826633; hg19: chr7-27204785;