chr4-344411-G-C

Position:

• chr4-344411-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_003441.4(ZNF141):​c.207G>C​(p.Lys69Asn) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF141 NM_003441.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.892

Genes affected

ZNF141 (HGNC:12926): (zinc finger protein 141) The protein encoded by this gene is a zinc finger protein that may be a tumor suppressor. Defects in this gene have been associated with autosomal recessive postaxial polydactyly type A. [provided by RefSeq, Jan 2017]

ZNF141 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03967467).
• BP6: Variant 4-344411-G-C is Benign according to our data. Variant chr4-344411-G-C is described in ClinVar as [Benign]. Clinvar id is 3059090.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF141	NM_003441.4	c.207G>C	p.Lys69Asn	missense_variant	3/4	ENST00000240499.8	NP_003432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF141	ENST00000240499.8	c.207G>C	p.Lys69Asn	missense_variant	3/4	1	NM_003441.4	ENSP00000240499.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.219 Hom.: 0

ExAC AF: 0.00115 AC: 140

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ZNF141-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Uncertain	0.97
DEOGEN2	Benign	0.062	.;.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.16	T;T;T
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.40	.;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.025
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.046	D;D;T
Polyphen		0.094	B;P;B
Vest4		0.26
MutPred		0.47		Gain of ubiquitination at K66 (P = 0.0289);Gain of ubiquitination at K66 (P = 0.0289);Gain of ubiquitination at K66 (P = 0.0289);
MVP		0.13
MPC		0.078
ClinPred		0.15	T
GERP RS		0.12
Varity_R		0.23
gMVP		0.012

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

Publications

LitVar

Other links and lift over

dbSNP: rs79869819; hg19: chr4-338200; COSMIC: COSV53659646; COSMIC: COSV53659646;