4-343890-A-G

Position:

• chr4-343890-A-G

Variant summary

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

The ENST00000240499.8(ZNF141):​c.112A>G​(p.Arg38Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.9e-7 (0 hom.)
• Consequence: ZNF141 ENST00000240499.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.75

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=0.13057745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF141	NM_003441.4	c.112A>G	p.Arg38Gly	missense_variant	2/4	ENST00000240499.8	NP_003432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF141	ENST00000240499.8	c.112A>G	p.Arg38Gly	missense_variant	2/4	1	NM_003441.4	ENSP00000240499.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453186 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722818

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

Jun 17, 2024

The c.112A>G (p.R38G) alteration is located in exon 2 (coding exon 2) of the ZNF141 gene. This alteration results from a A to G substitution at nucleotide position 112, causing the arginine (R) at amino acid position 38 to be replaced by a glycine (G). 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	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	.;.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.034	T;T;T
M_CAP	Benign	0.00073	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	.;.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.0	D;D;D
REVEL	Benign	0.082
Sift	Benign	0.038	D;D;D
Sift4G	Benign	0.15	T;T;T
Polyphen		1.0	D;B;D
Vest4		0.29
MutPred		0.60		Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);
MVP		0.28
MPC		0.38
ClinPred		0.80	D
GERP RS		-2.2
Varity_R		0.28
gMVP		0.034

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: rs1553848975; hg19: chr4-337679;