19-34740795-C-G

Variant names:

• chr19-34740795-C-G
• NM_001029997.4:c.414C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001029997.4(ZNF181):​c.414C>G​(p.Phe138Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. 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: 0.383
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057473898).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029997.4. 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
	ZNF181	NM_001029997.4	MANE Select	c.414C>G	p.Phe138Leu	missense	Exon 4 of 4	NP_001025168.2	Q2M3W8-1
	ZNF181	NM_001145665.2		c.411C>G	p.Phe137Leu	missense	Exon 4 of 4	NP_001139137.1	Q2M3W8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF181	ENST00000492450.3	TSL:1 MANE Select	c.414C>G	p.Phe138Leu	missense	Exon 4 of 4	ENSP00000420727.1	Q2M3W8-1
	ZNF181	ENST00000459757.6	TSL:1	c.411C>G	p.Phe137Leu	missense	Exon 4 of 4	ENSP00000419435.1	Q2M3W8-3
	ZNF181	ENST00000392232.7	TSL:5	c.546C>G	p.Phe182Leu	missense	Exon 6 of 6	ENSP00000376065.3	F8W889

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.8
DANN	Benign	0.30
DEOGEN2	Benign	0.062	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.38
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.013
Sift	Benign	0.63	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.24		Loss of helix (P = 0.1299)
MVP		0.23
MPC		0.26
ClinPred		0.016	T
GERP RS		-0.41
Varity_R		0.067
gMVP		0.094
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr19-35231700;