chr9-16419273-C-T

Variant names:

• chr9-16419273-C-T
• rs1199209096
• NM_017637.6:c.3016G>A

Variant summary

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

The NM_017637.6(BNC2):​c.3016G>A​(p.Ala1006Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1006V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BNC2 NM_017637.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

Genes affected

BNC2 (HGNC:30988): (basonuclin zinc finger protein 2) This gene encodes a conserved zinc finger protein. The encoded protein functions in skin color saturation. Mutations in this gene are associated with facial pigmented spots. This gene is also associated with susceptibility to adolescent idiopathic scoliosis. [provided by RefSeq, Jul 2016]

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=0.0772059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC2	NM_017637.6	c.3016G>A	p.Ala1006Thr	missense_variant	Exon 7 of 7	ENST00000380672.9	NP_060107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNC2	ENST00000380672.9	c.3016G>A	p.Ala1006Thr	missense_variant	Exon 7 of 7	2	NM_017637.6	ENSP00000370047.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3016G>A (p.A1006T) alteration is located in exon 7 (coding exon 7) of the BNC2 gene. This alteration results from a G to A substitution at nucleotide position 3016, causing the alanine (A) at amino acid position 1006 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.035	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.030
Sift	Benign	0.19	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0020	B;.
Vest4		0.020
MutPred		0.34		Gain of phosphorylation at A1006 (P = 0.005);.;
MVP		0.093
MPC		0.13
ClinPred		0.41	T
GERP RS		5.2
Varity_R		0.080
gMVP		0.29

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: rs1199209096; hg19: chr9-16419271;