19-34739544-C-A

Variant names:

• chr19-34739544-C-A
• NM_001029997.4:c.152C>A

Variant summary

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

The NM_001029997.4(ZNF181):​c.152C>A​(p.Pro51Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF181 NM_001029997.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.967

Genes affected

ZNF181 (HGNC:12971): (zinc finger protein 181) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See MIM 604749 for additional information on zinc finger proteins.[supplied by OMIM, Jul 2003]

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 rank	MANE	Protein	UniProt
ZNF181	NM_001029997.4	c.152C>A	p.Pro51Gln	missense_variant	Exon 3 of 4	ENST00000492450.3	NP_001025168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF181	ENST00000492450.3	c.152C>A	p.Pro51Gln	missense_variant	Exon 3 of 4	1	NM_001029997.4	ENSP00000420727.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152C>A (p.P51Q) alteration is located in exon 3 (coding exon 3) of the ZNF181 gene. This alteration results from a C to A substitution at nucleotide position 152, causing the proline (P) at amino acid position 51 to be replaced by a glutamine (Q). 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	0.97
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;.;T;.;.;T
Eigen	Uncertain	0.40
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.83	T;T;T;T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Uncertain	0.57	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	.;.;.;.;.;M
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-6.4	.;D;.;.;D;D
REVEL	Benign	0.082
Sift	Pathogenic	0.0	.;D;.;.;D;D
Sift4G	Uncertain	0.025	D;D;D;D;D;D
Polyphen		1.0	.;.;.;.;.;D
Vest4		0.52, 0.40, 0.42
MutPred		0.60		.;.;.;Gain of catalytic residue at P51 (P = 0.0404);.;Gain of catalytic residue at P51 (P = 0.0404);
MVP		0.88
MPC		0.79
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.52
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35230449;