9-132582846-G-T

Variant names:

• chr9-132582846-G-T
• rs73659100
• NM_020064.4:c.49G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020064.4(BARHL1):​c.49G>T​(p.Ala17Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A17T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BARHL1 NM_020064.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11602846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARHL1	NM_020064.4	c.49G>T	p.Ala17Ser	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.49G>T	p.Ala17Ser	missense_variant	Exon 1 of 3	1	NM_020064.4	ENSP00000263610.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249722 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135114

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456298 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723672

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.45
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.81	.;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	-0.14	N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.060	N;N
REVEL	Benign	0.23
Sift	Benign	0.75	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.031	B;B
Vest4		0.12
MutPred		0.11		Gain of phosphorylation at A17 (P = 0.0219);Gain of phosphorylation at A17 (P = 0.0219);
MVP		0.92
MPC		0.83
ClinPred		0.15	T
GERP RS		4.1
Varity_R		0.15
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs73659100; hg19: chr9-135458233;