rs10259620

Variant names:

• chr7-27162670-A-G
• rs10259620
• NM_152739.4:c.*933T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-27162670-A-G
• chr7-27162670-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152739.4(HOXA9):​c.*933T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 209,434 control chromosomes in the GnomAD database, including 56,481 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (39752 hom., cov: 33)
  • Exomes 𝑓: 0.76 (16729 hom.)
• Consequence: HOXA9 NM_152739.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 35 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

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.*933T>C		3_prime_UTR	Exon 2 of 2	NP_689952.1	P31269
	HOXA10-HOXA9	NM_001433944.1		c.*933T>C		3_prime_UTR	Exon 3 of 3	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.*933T>C		3_prime_UTR	Exon 2 of 2	ENSP00000343619.6	P31269
	HOXA10-HOXA9	ENST00000470747.5	TSL:3	c.*933T>C		3_prime_UTR	Exon 3 of 3	ENSP00000421799.3
	HOXA9	ENST00000497089.1	TSL:1	n.1323T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109242 AN: 152012 Hom.: 39732 Cov.: 33

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.751

GnomAD4 exome AF: 0.761 AC: 43616 AN: 57304 Hom.: 16729 Cov.: 0 AF XY: 0.764 AC XY: 20425 AN XY: 26744

African (AFR) AF: 0.642 AC: 1591 AN: 2478

American (AMR) AF: 0.693 AC: 1132 AN: 1634

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 3055 AN: 3656

East Asian (EAS) AF: 0.678 AC: 5832 AN: 8598

South Asian (SAS) AF: 0.854 AC: 420 AN: 492

European-Finnish (FIN) AF: 0.708 AC: 327 AN: 462

Middle Eastern (MID) AF: 0.810 AC: 269 AN: 332

European-Non Finnish (NFE) AF: 0.786 AC: 27381 AN: 34822

Other (OTH) AF: 0.747 AC: 3609 AN: 4830

GnomAD4 genome AF: 0.719 AC: 109312 AN: 152130 Hom.: 39752 Cov.: 33 AF XY: 0.717 AC XY: 53296 AN XY: 74382

African (AFR) AF: 0.613 AC: 25397 AN: 41458

American (AMR) AF: 0.702 AC: 10735 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2974 AN: 3472

East Asian (EAS) AF: 0.633 AC: 3275 AN: 5176

South Asian (SAS) AF: 0.825 AC: 3973 AN: 4818

European-Finnish (FIN) AF: 0.707 AC: 7484 AN: 10590

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53041 AN: 68008

Other (OTH) AF: 0.751 AC: 1585 AN: 2110

Alfa AF: 0.761 Hom.: 172056

Bravo AF: 0.708

Asia WGS AF: 0.733 AC: 2550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0040
DANN	Benign	0.33
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10259620; hg19: chr7-27202289; COSMIC: COSV58656472; COSMIC: COSV58656472;