9-132583132-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020064.4(BARHL1):​c.335C>A​(p.Ala112Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

BARHL1
NM_020064.4 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31
Variant links:
Genes affected
BARHL1 (HGNC:953): (BarH like homeobox 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including negative regulation of neuron apoptotic process; nervous system development; and sensory perception of sound. Predicted to be part of chromatin. Predicted to be active in nucleus. Biomarker of Alzheimer's disease; high grade glioma; and triple-receptor negative breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BARHL1NM_020064.4 linkc.335C>A p.Ala112Glu missense_variant Exon 1 of 3 ENST00000263610.7 NP_064448.1 Q9BZE3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BARHL1ENST00000263610.7 linkc.335C>A p.Ala112Glu missense_variant Exon 1 of 3 1 NM_020064.4 ENSP00000263610.2 Q9BZE3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.335C>A (p.A112E) alteration is located in exon 1 (coding exon 1) of the BARHL1 gene. This alteration results from a C to A substitution at nucleotide position 335, causing the alanine (A) at amino acid position 112 to be replaced by a glutamic acid (E). 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
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T;T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Benign
0.54
D
LIST_S2
Pathogenic
0.97
.;D
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Uncertain
0.23
D
MutationAssessor
Benign
1.9
L;L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-1.4
N;N
REVEL
Uncertain
0.57
Sift
Uncertain
0.0070
D;D
Sift4G
Benign
0.072
T;T
Polyphen
0.21
B;B
Vest4
0.81
MutPred
0.20
Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);
MVP
0.94
MPC
1.9
ClinPred
0.92
D
GERP RS
4.2
Varity_R
0.44
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs986962758; hg19: chr9-135458519; API