15-83257959-C-T

Variant names:

• chr15-83257959-C-T
• rs377137350
• NM_001717.4:c.2468G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001717.4(BNC1):​c.2468G>A​(p.Gly823Glu) 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. 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. G823A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BNC1 NM_001717.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.91
• Publications: 0 publications found

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]

BNC1 Gene-Disease associations (from GenCC):

• premature ovarian failure 16

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259986 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33472562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001717.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC1	NM_001717.4	MANE Select	c.2468G>A	p.Gly823Glu	missense	Exon 5 of 5	NP_001708.3
	BNC1	NM_001301206.2		c.2447G>A	p.Gly816Glu	missense	Exon 5 of 5	NP_001288135.1	F5GY04

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC1	ENST00000345382.7	TSL:1 MANE Select	c.2468G>A	p.Gly823Glu	missense	Exon 5 of 5	ENSP00000307041.2	Q01954
	BNC1	ENST00000569704.2	TSL:5	c.2447G>A	p.Gly816Glu	missense	Exon 5 of 5	ENSP00000456727.1	F5GY04
	ENSG00000259986	ENST00000565495.1	TSL:5	n.264+72891C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.40
Sift	Benign	0.058	T
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.56		Gain of sheet (P = 0.0221)
MVP		0.19
MPC		0.72
ClinPred		0.88	D
GERP RS		5.9
Varity_R		0.35
gMVP		0.68

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

Other links and lift over

dbSNP: rs377137350; hg19: chr15-83926711;