Variant 11-122981640-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001098169.2(BSX):c.32C>T(p.Pro11Leu) variant causes a missense change. 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BSX
NM_001098169.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Variant links:

Genes affected

BSX (HGNC:20450): (brain specific homeobox) 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 eating behavior; mammary gland involution; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

BSX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2664775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSX	NM_001098169.2 linkuse as main transcript	c.32C>T	p.Pro11Leu	missense_variant	1/3	ENST00000343035.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSX	ENST00000343035.3 linkuse as main transcript	c.32C>T	p.Pro11Leu	missense_variant	1/3	5	NM_001098169.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000186

AC:

AN:

214536

Hom.:

AF XY:

0.0000172

AC XY:

AN XY:

116152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000972

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000373

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000346

AC:

AN:

1443266

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

716034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000717

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000241

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000829

AC:

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

Aug 08, 2022

The c.32C>T (p.P11L) alteration is located in exon 1 (coding exon 1) of the BSX gene. This alteration results from a C to T substitution at nucleotide position 32, causing the proline (P) at amino acid position 11 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.15

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.043

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.82

M_CAP

Benign

0.082

MetaRNN

Benign

0.27

MetaSVM

Uncertain

0.054

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.27

Sift

Uncertain

0.018

Sift4G

Benign

0.21

Polyphen

0.43

Vest4

0.48

MutPred

0.36

Loss of disorder (P = 0.0283);

MVP

0.88

MPC

0.83

ClinPred

0.33

GERP RS

4.6

Varity_R

0.097

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over