Genetic Variant BHLHE22:p.Gly109Ser (chr8-64581115-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152414.5(BHLHE22):c.325G>A(p.Gly109Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G109D) 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.855

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34893617).

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.325G>A	p.Gly109Ser	missense	Exon 1 of 1	NP_689627.1	Q8NFJ8
	BHLHE22-AS1	NR_152770.1		n.175+603C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BHLHE22	ENST00000321870.3	TSL:6 MANE Select	c.325G>A	p.Gly109Ser	missense	Exon 1 of 1	ENSP00000318799.1	Q8NFJ8
BHLHE22-AS1	ENST00000517909.1	TSL:2	n.171+603C>T		intron	N/A
BHLHE22-AS1	ENST00000665275.1		n.94+603C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1216844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

590312

African (AFR)

AF:

0.00

AC:

AN:

24822

American (AMR)

AF:

0.00

AC:

AN:

13340

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16700

East Asian (EAS)

AF:

0.00

AC:

AN:

29234

South Asian (SAS)

AF:

0.00

AC:

AN:

47774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1001520

Other (OTH)

AF:

0.00

AC:

AN:

49922

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.063

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.35

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

1.1

PhyloP100

0.85

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.56

REVEL

Uncertain

0.31

Sift

Uncertain

0.025

Sift4G

Benign

0.12

Polyphen

0.99

Vest4

0.052

MutPred

0.12

Gain of glycosylation at G109 (P = 0.018)

MVP

0.47

MPC

2.0

ClinPred

0.55

GERP RS

2.0

Varity_R

0.11

gMVP

0.36

Mutation Taster

=85/15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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