10-43616533-G-C

Position:

• chr10-43616533-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145312.4(ZNF485):​c.490G>C​(p.Gly164Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ZNF485 NM_145312.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

Genes affected

ZNF485 (HGNC:23440): (zinc finger protein 485) Predicted to enable DNA-binding transcription activator 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38869208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF485	NM_145312.4	c.490G>C	p.Gly164Arg	missense_variant	5/5	ENST00000361807.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF485	ENST00000361807.8	c.490G>C	p.Gly164Arg	missense_variant	5/5	1	NM_145312.4	P1
ZNF485	ENST00000374435.3	c.490G>C	p.Gly164Arg	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

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 07, 2021

The c.490G>C (p.G164R) alteration is located in exon 5 (coding exon 4) of the ZNF485 gene. This alteration results from a G to C substitution at nucleotide position 490, causing the glycine (G) at amino acid position 164 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;M
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.99	D;D
Vest4		0.23
MutPred		0.68		Gain of disorder (P = 0.1151);Gain of disorder (P = 0.1151);
MVP		0.54
MPC		0.63
ClinPred		0.98	D
GERP RS		2.5
Varity_R		0.42
gMVP		0.023

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: chr10-44111981;