4-372877-G-A

Position:

• chr4-372877-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003441.4(ZNF141):​c.440G>A​(p.Cys147Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZNF141 NM_003441.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.207

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19398007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF141	NM_003441.4	c.440G>A	p.Cys147Tyr	missense_variant	4/4	ENST00000240499.8	NP_003432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF141	ENST00000240499.8	c.440G>A	p.Cys147Tyr	missense_variant	4/4	1	NM_003441.4	ENSP00000240499.7
ZNF141	ENST00000512994.5	c.440G>A	p.Cys147Tyr	missense_variant	4/5	1		ENSP00000425799.1
ZNF141	ENST00000505939.5	c.227-10218G>A		intron_variant		5		ENSP00000424403.1
ZNF141	ENST00000366506.4	n.387G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461036 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2024

The c.440G>A (p.C147Y) alteration is located in exon 4 (coding exon 4) of the ZNF141 gene. This alteration results from a G to A substitution at nucleotide position 440, causing the cysteine (C) at amino acid position 147 to be replaced by a tyrosine (Y). 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	Benign	0.089
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.29	.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-9.3	D;D
REVEL	Benign	0.034
Sift	Benign	0.12	T;T
Sift4G	Uncertain	0.045	D;D
Polyphen		0.99	D;D
Vest4		0.20
MutPred		0.46		Loss of methylation at K148 (P = 0.0277);Loss of methylation at K148 (P = 0.0277);
MVP		0.23
MPC		0.50
ClinPred		0.87	D
GERP RS		-1.8
Varity_R		0.21
gMVP		0.035

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-366666;