Variant 8-64581346-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152414.5(BHLHE22):c.556A>G(p.Asn186Asp) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 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: 1.35

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 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=0.21105337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHLHE22	NM_152414.5 linkuse as main transcript	c.556A>G	p.Asn186Asp	missense_variant	1/1	ENST00000321870.3
BHLHE22-AS1	NR_152770.1 linkuse as main transcript	n.175+372T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BHLHE22	ENST00000321870.3 linkuse as main transcript	c.556A>G	p.Asn186Asp	missense_variant	1/1		NM_152414.5	P1
BHLHE22-AS1	ENST00000517909.1 linkuse as main transcript	n.171+372T>C		intron_variant, non_coding_transcript_variant		2
BHLHE22-AS1	ENST00000665275.1 linkuse as main transcript	n.94+372T>C		intron_variant, non_coding_transcript_variant
BHLHE22-AS1	ENST00000670034.1 linkuse as main transcript	n.204+372T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1317218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

647072

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:

0.00

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

Dec 11, 2023

The c.556A>G (p.N186D) alteration is located in exon 1 (coding exon 1) of the BHLHE22 gene. This alteration results from a A to G substitution at nucleotide position 556, causing the asparagine (N) at amino acid position 186 to be replaced by an aspartic acid (D). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.46

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Benign

0.55

Polyphen

0.61

Vest4

0.15

MutPred

0.25

Gain of catalytic residue at N186 (P = 0.077);

MVP

0.14

MPC

1.5

ClinPred

0.25

GERP RS

3.5

Varity_R

0.33

gMVP

0.13

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