chr12-48343722-C-G

Position:

• chr12-48343722-C-G

Variant summary

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

The NM_001172681.2(ZNF641):​c.526G>C​(p.Gly176Arg) 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. 13/21 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)
• Consequence: ZNF641 NM_001172681.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

Genes affected

ZNF641 (HGNC:31834): (zinc finger protein 641) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06717491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF641	NM_001172681.2	c.526G>C	p.Gly176Arg	missense_variant	6/6	ENST00000547026.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF641	ENST00000547026.6	c.526G>C	p.Gly176Arg	missense_variant	6/6	1	NM_001172681.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jun 29, 2023

The c.568G>C (p.G190R) alteration is located in exon 7 (coding exon 6) of the ZNF641 gene. This alteration results from a G to C substitution at nucleotide position 568, causing the glycine (G) at amino acid position 190 to be replaced by an arginine (R). 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	0.26
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T;T;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.067	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.58	N;N;.;.
MutationTaster	Benign	0.90	D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.050	N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.61	T;T;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.0050	B;B;.;.
Vest4		0.35
MutPred		0.21		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;.;
MVP		0.37
MPC		0.94
ClinPred		0.35	T
GERP RS		4.5
Varity_R		0.10
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-48737505;