15-83257837-T-A

Variant names:

• chr15-83257837-T-A
• NM_001717.4:c.2590A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001717.4(BNC1):​c.2590A>T​(p.Met864Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BNC1 NM_001717.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.536

Genes affected

BNC1 (HGNC:1081): (basonuclin zinc finger protein 1) This gene encodes a zinc finger protein present in the basal cell layer of the epidermis and in hair follicles. It is also found in abundance in the germ cells of testis and ovary. This protein is thought to play a regulatory role in keratinocyte proliferation and it may also be a regulator for rRNA transcription. Disruption of this gene has been implicated in premature ovarian failure as well as testicular premature aging. [provided by RefSeq, Sep 2020]

ENSG00000259986 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030694991).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC1	NM_001717.4	c.2590A>T	p.Met864Leu	missense_variant	Exon 5 of 5	ENST00000345382.7	NP_001708.3
BNC1	NM_001301206.2	c.2569A>T	p.Met857Leu	missense_variant	Exon 5 of 5		NP_001288135.1
BNC1	XM_011521893.2	c.2515A>T	p.Met839Leu	missense_variant	Exon 5 of 5		XP_011520195.1
BNC1	XM_011521894.1	c.2236A>T	p.Met746Leu	missense_variant	Exon 4 of 4		XP_011520196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNC1	ENST00000345382.7	c.2590A>T	p.Met864Leu	missense_variant	Exon 5 of 5	1	NM_001717.4	ENSP00000307041.2
BNC1	ENST00000569704.2	c.2569A>T	p.Met857Leu	missense_variant	Exon 5 of 5	5		ENSP00000456727.1
ENSG00000259986	ENST00000565495.1	n.264+72769T>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2590A>T (p.M864L) alteration is located in exon 5 (coding exon 5) of the BNC1 gene. This alteration results from a A to T substitution at nucleotide position 2590, causing the methionine (M) at amino acid position 864 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	0.086
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.087	T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.031	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.021
Sift	Benign	0.97	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0020	B;B
Vest4		0.17
MutPred		0.16		Gain of methylation at K865 (P = 0.0316);.;
MVP		0.043
MPC		0.13
ClinPred		0.16	T
GERP RS		1.1
Varity_R		0.067
gMVP		0.22

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: chr15-83926589;