ENST00000415784.6:c.-338A>T

Variant names:

• chr19-19677883-A-T
• rs949046289
• ENST00000415784.6:c.-338A>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The ENST00000415784.6(ZNF101):​c.-338A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZNF101 ENST00000415784.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415784.6. 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
	ZNF101	NM_033204.4	MANE Select	c.23A>T	p.Asp8Val	missense	Exon 2 of 4	NP_149981.2
	ZNF101	NM_001300949.2		c.-334A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	NP_001287878.1	Q8IZC7-2
	ZNF101	NM_001300949.2		c.-334A>T		5_prime_UTR	Exon 2 of 4	NP_001287878.1	Q8IZC7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF101	ENST00000415784.6	TSL:1	c.-338A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	ENSP00000400952.2	Q8IZC7-2
	ZNF101	ENST00000592502.2	TSL:1 MANE Select	c.23A>T	p.Asp8Val	missense	Exon 2 of 4	ENSP00000468049.1	Q8IZC7-1
	ZNF101	ENST00000444249.6	TSL:1	c.23A>T	p.Asp8Val	missense	Exon 2 of 4	ENSP00000466697.1	Q504T0

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0078	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	4.7	H
PhyloP100		3.4
PrimateAI	Benign	0.33	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.81		Loss of disorder (P = 0.0572)
MVP		0.48
MPC		1.1
ClinPred		0.97	D
GERP RS		0.23
Varity_R		0.82
gMVP		0.57
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs949046289; hg19: chr19-19788692;