Variant chr10-92694637-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000282728.10(HHEX):c.682G>C(p.Gly228Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,816 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HHEX
ENST00000282728.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66

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:

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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=0.22503793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHEX	NM_002729.5 linkuse as main transcript	c.682G>C	p.Gly228Arg	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.682G>C	p.Gly228Arg	missense_variant	4/4	1	NM_002729.5	ENSP00000282728.5	Q03014
HHEX	ENST00000492654.3 linkuse as main transcript	c.166G>C	p.Gly56Arg	missense_variant	3/3	1		ENSP00000447953.1	F8VU08
HHEX	ENST00000472590.6 linkuse as main transcript	c.166G>C	p.Gly56Arg	missense_variant	4/4	2		ENSP00000450017.1	F8VU08

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727206

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Mar 22, 2023

The c.682G>C (p.G228R) alteration is located in exon 4 (coding exon 4) of the HHEX gene. This alteration results from a G to C substitution at nucleotide position 682, causing the glycine (G) at amino acid position 228 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;T;T

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.61

T;.;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.66

P;.;.

Vest4

0.12

MutPred

0.29

Gain of solvent accessibility (P = 0.0097);.;.;

MVP

0.97

MPC

0.94

ClinPred

0.93

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over