Variant 7-27173468-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018951.4(HOXA10):c.839G>A(p.Cys280Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOXA10
NM_018951.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

HOXA10 (HGNC:5100): (homeobox A10) 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 that may regulate gene expression, morphogenesis, and differentiation. More specifically, it may function in fertility, embryo viability, and regulation of hematopoietic lineage commitment. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the downstream homeobox A9 (HOXA9) gene. [provided by RefSeq, Mar 2011]

HOXA10 links:

ENSG00000257184 (HGNC:):

ENSG00000257184 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA10	NM_018951.4 linkuse as main transcript	c.839G>A	p.Cys280Tyr	missense_variant	1/2	ENST00000283921.5	NP_061824.3	P31260-1
HOXA10	NR_037939.2 linkuse as main transcript	n.217-1295G>A		intron_variant
HOXA10-HOXA9	NR_037940.1 linkuse as main transcript	n.616+6178G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HOXA10	ENST00000283921.5 linkuse as main transcript	c.839G>A	p.Cys280Tyr	missense_variant	1/2	1	NM_018951.4	ENSP00000283921.4	P31260-1
ENSG00000257184	ENST00000470747.4 linkuse as main transcript	c.10+6178G>A		intron_variant		3		ENSP00000421799.3	D6RAR5
HOXA10	ENST00000396344.4 linkuse as main transcript	c.11-1295G>A		intron_variant		1		ENSP00000379633.4	P31260-2
HOXA9	ENST00000465941.1 linkuse as main transcript	n.479+1234G>A		intron_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

168436

Hom.:

AF XY:

0.0000106

AC XY:

AN XY:

94118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000284

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000212

AC:

AN:

1416240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701832

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000291

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.839G>A (p.C280Y) alteration is located in exon 1 (coding exon 1) of the HOXA10 gene. This alteration results from a G to A substitution at nucleotide position 839, causing the cysteine (C) at amino acid position 280 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.74

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-2.2

REVEL

Benign

0.20

Sift

Benign

0.040

Sift4G

Uncertain

0.049

Polyphen

0.95

Vest4

0.72

MutPred

0.24

Gain of phosphorylation at C280 (P = 0.0167);

MVP

0.44

ClinPred

0.41

GERP RS

4.7

Varity_R

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over