chr4-344414-C-G

Position:

• chr4-344414-C-G

Variant summary

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

The NM_003441.4(ZNF141):​c.210C>G​(p.Ile70Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,453,934 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: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF141 NM_003441.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.20

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049309462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF141	NM_003441.4	c.210C>G	p.Ile70Met	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.210C>G	p.Ile70Met	missense_variant	3/4	1	NM_003441.4	ENSP00000240499.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1453934 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 723342

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: 0.00000633

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Apr 01, 2024

The c.210C>G (p.I70M) alteration is located in exon 3 (coding exon 3) of the ZNF141 gene. This alteration results from a C to G substitution at nucleotide position 210, causing the isoleucine (I) at amino acid position 70 to be replaced by a methionine (M). 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	0.079
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0050
DANN	Benign	0.82
DEOGEN2	Benign	0.041	.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.099	T;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	.;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.8	N;N;N
REVEL	Benign	0.041
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.82	P;P;B
Vest4		0.21
MutPred		0.37		Gain of catalytic residue at I70 (P = 0.0203);Gain of catalytic residue at I70 (P = 0.0203);Gain of catalytic residue at I70 (P = 0.0203);
MVP		0.048
MPC		0.071
ClinPred		0.16	T
GERP RS		0.12
Varity_R		0.068
gMVP		0.0090

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-338203;