11-122977783-G-A

Variant summary

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

The NM_001098169.2(BSX):c.568C>T(p.Arg190Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,200 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BSX NM_001098169.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07

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]

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=0.18329361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSX	NM_001098169.2	c.568C>T	p.Arg190Cys	missense_variant	3/3	ENST00000343035.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSX	ENST00000343035.3	c.568C>T	p.Arg190Cys	missense_variant	3/3	5	NM_001098169.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461200 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726916

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.568C>T (p.R190C) alteration is located in exon 3 (coding exon 3) of the BSX gene. This alteration results from a C to T substitution at nucleotide position 568, causing the arginine (R) at amino acid position 190 to be replaced by a cysteine (C). 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	0.11
BayesDel_addAF	Benign	0.0070	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.092	D
MutationAssessor	Benign	0.61	N
MutationTaster	Benign	0.68	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.27
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.053	T
Polyphen		0.73	P
Vest4		0.14
MutPred		0.20		Gain of catalytic residue at P189 (P = 0.0069);
MVP		0.88
MPC		1.0
ClinPred		0.72	D
GERP RS		4.5
Varity_R		0.096
gMVP		0.58

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

Other links and lift over

dbSNP: rs1009896463; hg19: chr11-122848491;