NM_001207067.2:c.998C>T

Variant names:

• chr2-200820013-C-T
• rs765964327
• NM_001207067.2:c.998C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001207067.2(BZW1):​c.998C>T​(p.Thr333Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000456 in 1,536,068 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T333S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: BZW1 NM_001207067.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2980843).

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.998C>T	p.Thr333Ile	missense	Exon 10 of 12	NP_001193996.1	Q7L1Q6-1
	BZW1	NM_001207068.3		c.1094C>T	p.Thr365Ile	missense	Exon 10 of 12	NP_001193997.1	Q7L1Q6-3
	BZW1	NM_001207069.2		c.1010C>T	p.Thr337Ile	missense	Exon 10 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.998C>T	p.Thr333Ile	missense	Exon 10 of 12	ENSP00000386474.1	Q7L1Q6-1
	BZW1	ENST00000452790.6	TSL:2	c.1094C>T	p.Thr365Ile	missense	Exon 10 of 12	ENSP00000394316.2	Q7L1Q6-3
	BZW1	ENST00000409226.5	TSL:2	c.1010C>T	p.Thr337Ile	missense	Exon 10 of 12	ENSP00000386837.1	Q7L1Q6-4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000661 AC: 1 AN: 151308 AF XY: 0.0000126

Gnomad AFR exome AF: 0.000119

Gnomad AMR exome AF: 0.00

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 AF: 0.00000217 AC: 3 AN: 1383856 Hom.: 0 Cov.: 30 AF XY: 0.00000294 AC XY: 2 AN XY: 681302

African (AFR) AF: 0.0000969 AC: 3 AN: 30972

American (AMR) AF: 0.00 AC: 0 AN: 32972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24676

East Asian (EAS) AF: 0.00 AC: 0 AN: 35624

South Asian (SAS) AF: 0.00 AC: 0 AN: 76540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4382

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071840

Other (OTH) AF: 0.00 AC: 0 AN: 57402

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74368

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000724 AC: 3 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00921106), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.010	D
Sift4G	Benign	0.12	T
Polyphen		0.0010	B
Vest4		0.35
MutPred		0.40		Loss of disorder (P = 0.0494)
MVP		0.52
MPC		1.5
ClinPred		0.52	D
GERP RS		5.8
Varity_R		0.28
gMVP		0.24
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs765964327; hg19: chr2-201684736;