chr7-27147640-G-T

Position:

chr7-27147640-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024014.4(HOXA6):c.110C>A(p.Pro37His) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HOXA6
NM_024014.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48

Variant links:

Genes affected

HOXA6 (HGNC:5107): (homeobox A6) 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. [provided by RefSeq, Jul 2008]

HOXA6 links:

HOXA3 (HGNC:5104): (homeobox A3) 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. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HOXA3 links:

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

HOXA-AS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08245742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HOXA6	NM_024014.4 linkuse as main transcript	c.110C>A	p.Pro37His	missense_variant	1/2	ENST00000222728.3
HOXA3	NM_153631.3 linkuse as main transcript	c.-494+4648C>A		intron_variant		ENST00000612286.5
HOXA-AS3	NR_038832.1 linkuse as main transcript	n.177-3935G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HOXA6	ENST00000222728.3 linkuse as main transcript	c.110C>A	p.Pro37His	missense_variant	1/2	1	NM_024014.4	P1
HOXA3	ENST00000612286.5 linkuse as main transcript	c.-494+4648C>A		intron_variant		2	NM_153631.3	P1
HOXA-AS3	ENST00000518848.5 linkuse as main transcript	n.173-3935G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.110C>A (p.P37H) alteration is located in exon 1 (coding exon 1) of the HOXA6 gene. This alteration results from a C to A substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 to be replaced by a histidine (H). 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

0.073

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.077

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.81

M_CAP

Benign

0.018

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.53

MutationAssessor

Benign

-2.8

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.61

PROVEAN

Benign

6.2

REVEL

Benign

0.26

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.22

MutPred

0.41

Loss of disorder (P = 0.0415);

MVP

0.82

MPC

0.38

ClinPred

0.29

GERP RS

4.1

Varity_R

0.14

gMVP

0.53

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