Genetic Variant NM_001137601.3:c.217G>A (chr14-104801414-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001137601.3(ZBTB42):c.217G>A(p.Ala73Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,395,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZBTB42
NM_001137601.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Publications

0 publications found

Variant links:

Genes affected

ZBTB42 (HGNC:32550): (zinc finger and BTB domain containing 42) The protein encoded by this gene is a member of the C2H2 zinc finger protein family. This protein is predicted to have a pox virus and zinc finger (POZ) domain at the N-terminus and four zinc finger domains at the C-terminus. In human and mouse, the protein localizes to the nuclei of skeletal muscle cells. Knockdown of this gene in zebrafish results in abnormal skeletal muscle development and myofibrillar disorganization. A novel homozygous variant of the human gene has been associated with lethal congenital contracture syndrome, an autosomal recessive disorder that results in muscle wasting. [provided by RefSeq, Mar 2015]

ZBTB42 Gene-Disease associations (from GenCC):

lethal congenital contracture syndrome 6
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ZBTB42 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137601.3. 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
	ZBTB42	NM_001137601.3	MANE Select	c.217G>A	p.Ala73Thr	missense	Exon 1 of 1	NP_001131073.1	B2RXF5
	ZBTB42	NM_001370342.1		c.217G>A	p.Ala73Thr	missense	Exon 2 of 2	NP_001357271.1	B2RXF5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB42	ENST00000342537.8	TSL:6 MANE Select	c.217G>A	p.Ala73Thr	missense	Exon 1 of 1	ENSP00000409107.2	B2RXF5
ZBTB42	ENST00000555360.1	TSL:1	c.217G>A	p.Ala73Thr	missense	Exon 2 of 2	ENSP00000450673.1	B2RXF5
ZBTB42	ENST00000962340.1		c.217G>A	p.Ala73Thr	missense	Exon 2 of 2	ENSP00000632399.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000693

AC:

AN:

144210

AF XY:

0.0000129

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1395978

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

688152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31550

American (AMR)

AF:

0.00

AC:

AN:

35606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25110

East Asian (EAS)

AF:

0.00

AC:

AN:

35666

South Asian (SAS)

AF:

0.00

AC:

AN:

79118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1077726

Other (OTH)

AF:

0.00

AC:

AN:

57878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

0.0023

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.49

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

-0.025

MutationAssessor

Uncertain

2.9

PhyloP100

6.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.47

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.98

Vest4

0.27

MutPred

0.52

Gain of catalytic residue at A75 (P = 0.0013)

MVP

0.35

ClinPred

0.95

GERP RS

2.9

PromoterAI

-0.0088

Neutral

(source)

Varity_R

0.38

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over