chr4-344340-G-A

Position:

• chr4-344340-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003441.4(ZNF141):​c.136G>A​(p.Ala46Thr) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF141 NM_003441.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.164

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0042029917).
• BP6: Variant 4-344340-G-A is Benign according to our data. Variant chr4-344340-G-A is described in ClinVar as [Benign]. Clinvar id is 3059756.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF141	NM_003441.4	c.136G>A	p.Ala46Thr	missense_variant	3/4	ENST00000240499.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF141	ENST00000240499.8	c.136G>A	p.Ala46Thr	missense_variant	3/4	1	NM_003441.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0131 Hom.: 0

ExAC AF: 0.0206 AC: 2505

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ZNF141-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 21, 2020

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	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.4
DANN	Benign	0.86
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.040	T;T;T
MetaRNN	Benign	0.0042	T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.024	B;B;B
Vest4		0.090
MPC		0.32
ClinPred		0.010	T
GERP RS		0.79
Varity_R		0.075
gMVP		0.012

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs75245145; hg19: chr4-338129; COSMIC: COSV53657618; COSMIC: COSV53657618;