Variant 10-92694659-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002729.5(HHEX):c.704A>C(p.Gln235Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000034 ( 0 hom. )

Consequence

HHEX
NM_002729.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

Variant links:

Genes affected

HHEX (HGNC:4901): (hematopoietically expressed homeobox) This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation. [provided by RefSeq, Jul 2008]

HHEX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37770128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHEX	NM_002729.5 linkuse as main transcript	c.704A>C	p.Gln235Pro	missense_variant	4/4	ENST00000282728.10	NP_002720.1	Q03014

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HHEX	ENST00000282728.10 linkuse as main transcript	c.704A>C	p.Gln235Pro	missense_variant	4/4	1	NM_002729.5	ENSP00000282728.5	Q03014
HHEX	ENST00000492654.3 linkuse as main transcript	c.188A>C	p.Gln63Pro	missense_variant	3/3	1		ENSP00000447953.1	F8VU08
HHEX	ENST00000472590.6 linkuse as main transcript	c.188A>C	p.Gln63Pro	missense_variant	4/4	2		ENSP00000450017.1	F8VU08

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00000342

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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:

0.0000378

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

Dec 30, 2023

The c.704A>C (p.Q235P) alteration is located in exon 4 (coding exon 4) of the HHEX gene. This alteration results from a A to C substitution at nucleotide position 704, causing the glutamine (Q) at amino acid position 235 to be replaced by a proline (P). 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

0.068

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

D;T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

T;.;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Uncertain

0.65

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.0070

D;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.34

MutPred

0.26

Gain of catalytic residue at Q235 (P = 0.01);.;.;

MVP

0.99

MPC

0.94

ClinPred

0.89

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.44

gMVP

0.36

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