Genetic Variant BHLHE22:p.Ala173Glu (chr8-64581308-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152414.5(BHLHE22):c.518C>A(p.Ala173Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A173V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BHLHE22
NM_152414.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.363

Publications

1 publications found

Variant links:

Genes affected

BHLHE22 (HGNC:11963): (basic helix-loop-helix family member e22) This gene encodes a protein that belongs to the basic helix-loop-helix (bHLH) family of transcription factors that regulate cell fate determination, proliferation, and differentiation. A similar protein in mouse is required for the development of the dorsal cochlear nuclei, and is thought to play a role in in the differentiation of neurons involved in sensory input. The mouse protein also functions in retinogenesis. [provided by RefSeq, Oct 2016]

BHLHE22 links:

BHLHE22-AS1 (HGNC:56147): (BHLHE22 antisense RNA 1)

BHLHE22-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16703871).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152414.5. 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
	BHLHE22	NM_152414.5	MANE Select	c.518C>A	p.Ala173Glu	missense	Exon 1 of 1	NP_689627.1	Q8NFJ8
	BHLHE22-AS1	NR_152770.1		n.175+410G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BHLHE22	ENST00000321870.3	TSL:6 MANE Select	c.518C>A	p.Ala173Glu	missense	Exon 1 of 1	ENSP00000318799.1	Q8NFJ8
BHLHE22-AS1	ENST00000517909.1	TSL:2	n.171+410G>T		intron	N/A
BHLHE22-AS1	ENST00000665275.1		n.94+410G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1278286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

626644

African (AFR)

AF:

0.00

AC:

AN:

25502

American (AMR)

AF:

0.00

AC:

AN:

16534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18908

East Asian (EAS)

AF:

0.00

AC:

AN:

30084

South Asian (SAS)

AF:

0.00

AC:

AN:

62210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1036936

Other (OTH)

AF:

0.00

AC:

AN:

52896

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.092

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.49

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.34

PhyloP100

0.36

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.20

REVEL

Benign

0.21

Sift

Uncertain

0.0070

Sift4G

Benign

0.12

Polyphen

0.0030

Vest4

0.21

MutPred

0.31

Gain of solvent accessibility (P = 0.0016)

MVP

0.10

MPC

1.2

ClinPred

0.24

GERP RS

2.6

Varity_R

0.18

gMVP

0.30

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over