NM_001207067.2:c.868C>T

Variant names:

• chr2-200818803-C-T
• rs776829596
• NM_001207067.2:c.868C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001207067.2(BZW1):​c.868C>T​(p.Pro290Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BZW1 NM_001207067.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• Publications: 0 publications found

Genes affected

BZW1 (HGNC:18380): (basic leucine zipper and W2 domains 1) Enables RNA binding activity and cadherin binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1818175).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207067.2. 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
	BZW1	NM_001207067.2	MANE Select	c.868C>T	p.Pro290Ser	missense	Exon 9 of 12	NP_001193996.1	Q7L1Q6-1
	BZW1	NM_001207068.3		c.964C>T	p.Pro322Ser	missense	Exon 9 of 12	NP_001193997.1	Q7L1Q6-3
	BZW1	NM_001207069.2		c.880C>T	p.Pro294Ser	missense	Exon 9 of 12	NP_001193998.1	Q7L1Q6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BZW1	ENST00000409600.6	TSL:1 MANE Select	c.868C>T	p.Pro290Ser	missense	Exon 9 of 12	ENSP00000386474.1	Q7L1Q6-1
	BZW1	ENST00000452790.6	TSL:2	c.964C>T	p.Pro322Ser	missense	Exon 9 of 12	ENSP00000394316.2	Q7L1Q6-3
	BZW1	ENST00000409226.5	TSL:2	c.880C>T	p.Pro294Ser	missense	Exon 9 of 12	ENSP00000386837.1	Q7L1Q6-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000171 AC: 4 AN: 233974 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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: 5 AN: 1445018 Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2 AN XY: 718740

African (AFR) AF: 0.00 AC: 0 AN: 32134

American (AMR) AF: 0.000129 AC: 5 AN: 38902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25530

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 82502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107712

Other (OTH) AF: 0.00 AC: 0 AN: 59742

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-0.34	N
PhyloP100		7.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.18
Sift	Benign	0.29	T
Sift4G	Benign	0.18	T
Polyphen		0.0020	B
Vest4		0.33
MutPred		0.34		Loss of catalytic residue at P290 (P = 0.0056)
MVP		0.35
MPC		0.95
ClinPred		0.23	T
GERP RS		5.6
PromoterAI		-0.014	Neutral
Varity_R		0.056
gMVP		0.22
Mutation Taster		=75/25	polymorphism

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: rs776829596; hg19: chr2-201683526;