NM_001137601.3:c.322T>C

Variant names:

• chr14-104801519-T-C
• NM_001137601.3:c.322T>C

Variant summary

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

The NM_001137601.3(ZBTB42):​c.322T>C​(p.Tyr108His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZBTB42 NM_001137601.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69
• Publications: 0 publications found

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)

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=0.30959532).

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.322T>C	p.Tyr108His	missense	Exon 1 of 1	NP_001131073.1	B2RXF5
	ZBTB42	NM_001370342.1		c.322T>C	p.Tyr108His	missense	Exon 2 of 2	NP_001357271.1	B2RXF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB42	ENST00000342537.8	TSL:6 MANE Select	c.322T>C	p.Tyr108His	missense	Exon 1 of 1	ENSP00000409107.2	B2RXF5
	ZBTB42	ENST00000555360.1	TSL:1	c.322T>C	p.Tyr108His	missense	Exon 2 of 2	ENSP00000450673.1	B2RXF5
	ZBTB42	ENST00000962340.1		c.322T>C	p.Tyr108His	missense	Exon 2 of 2	ENSP00000632399.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 90

GnomAD4 genome Cov.: 34

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	Pathogenic	0.92
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.36	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.70	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.34
Sift	Benign	0.073	T
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.53		Gain of catalytic residue at D109 (P = 0.0017)
MVP		0.19
ClinPred		0.79	D
GERP RS		3.0
PromoterAI		-0.014	Neutral
Varity_R		0.11
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr14-105267856;