12-48343688-T-C

Position:

• chr12-48343688-T-C

Variant summary

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

The NM_001172681.2(ZNF641):​c.560A>G​(p.Glu187Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 1,372,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: ZNF641 NM_001172681.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

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]

ZNF641 (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=0.17219532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF641	NM_001172681.2	c.560A>G	p.Glu187Gly	missense_variant	6/6	ENST00000547026.6	NP_001166152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF641	ENST00000547026.6	c.560A>G	p.Glu187Gly	missense_variant	6/6	1	NM_001172681.2	ENSP00000449974.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000656 AC: 9 AN: 1372546 Hom.: 0 Cov.: 32 AF XY: 0.0000119 AC XY: 8 AN XY: 673308

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: 0.00000842

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

Dec 28, 2023

The c.602A>G (p.E201G) alteration is located in exon 7 (coding exon 6) of the ZNF641 gene. This alteration results from a A to G substitution at nucleotide position 602, causing the glutamic acid (E) at amino acid position 201 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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.036	T;T;.;.
Eigen	Benign	-0.095
Eigen_PC	Benign	0.0050
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.77	.;T;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.052
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.035	D;D;T;D
Polyphen		0.28	B;B;.;.
Vest4		0.18
MutPred		0.34		Loss of solvent accessibility (P = 0.0036);Loss of solvent accessibility (P = 0.0036);.;.;
MVP		0.45
MPC		0.27
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.21
gMVP		0.26

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: chr12-48737471;