9-132583183-T-A

Variant names:

• chr9-132583183-T-A
• NM_020064.4:c.386T>A

Variant summary

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

The NM_020064.4(BARHL1):​c.386T>A​(p.Leu129His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BARHL1 NM_020064.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

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]

ACMG classification

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
BARHL1	NM_020064.4	c.386T>A	p.Leu129His	missense_variant	Exon 1 of 3	ENST00000263610.7	NP_064448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARHL1	ENST00000263610.7	c.386T>A	p.Leu129His	missense_variant	Exon 1 of 3	1	NM_020064.4	ENSP00000263610.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461120 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726834

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.386T>A (p.L129H) alteration is located in exon 1 (coding exon 1) of the BARHL1 gene. This alteration results from a T to A substitution at nucleotide position 386, causing the leucine (L) at amino acid position 129 to be replaced by a histidine (H). 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	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.67	.;T
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N;N
REVEL	Pathogenic	0.70
Sift	Benign	0.35	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.99	D;D
Vest4		0.38
MutPred		0.34		Gain of methylation at K132 (P = 0.0738);Gain of methylation at K132 (P = 0.0738);
MVP		0.95
MPC		1.6
ClinPred		0.69	D
GERP RS		4.2
Varity_R		0.26
gMVP		0.56

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.

Other links and lift over

hg19: chr9-135458570;