19-19677901-C-T

Position:

• chr19-19677901-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033204.4(ZNF101):​c.41C>T​(p.Thr14Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF101 NM_033204.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.414

Genes affected

ZNF101 (HGNC:12881): (zinc finger protein 101) Zinc finger proteins (ZNFs), such as ZNF101, bind nucleic acids and perform many key functions, the most important of which is regulating transcription (summary by Bellefroid et al., 1993 [PubMed 8467795]). See ZNF91 (MIM 603971) for general information on ZNFs.[supplied by OMIM, Nov 2010]

ZNF101 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF101	NM_033204.4	c.41C>T	p.Thr14Ile	missense_variant	2/4	ENST00000592502.2	NP_149981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF101	ENST00000592502.2	c.41C>T	p.Thr14Ile	missense_variant	2/4	1	NM_033204.4	ENSP00000468049.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460108 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726384

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2024

The c.41C>T (p.T14I) alteration is located in exon 2 (coding exon 2) of the ZNF101 gene. This alteration results from a C to T substitution at nucleotide position 41, causing the threonine (T) at amino acid position 14 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0035	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	.;M
PrimateAI	Benign	0.41	T
Sift4G	Uncertain	0.026	D;D
Polyphen		1.0	.;D
Vest4		0.38
MutPred		0.76		Gain of catalytic residue at T14 (P = 0.087);Gain of catalytic residue at T14 (P = 0.087);
MVP		0.41
MPC		0.91
ClinPred		0.95	D
GERP RS		0.23
Varity_R		0.43
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1434397471; hg19: chr19-19788710;