7-6617244-G-A

Position:

• chr7-6617244-G-A

Variant summary

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

The NM_017560.3(ZNF853):​c.67G>A​(p.Glu23Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,380,372 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: 0.000026 (0 hom.)
• Consequence: ZNF853 NM_017560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.179

Genes affected

ZNF853 (HGNC:21767): (zinc finger protein 853) 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. [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=0.067219555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF853	NM_017560.3	c.67G>A	p.Glu23Lys	missense_variant	2/3	ENST00000457543.4	NP_060030.1
ZNF853	NM_001353546.2	c.22G>A	p.Glu8Lys	missense_variant	2/3		NP_001340475.1
ZNF853	XM_011515438.4	c.67G>A	p.Glu23Lys	missense_variant	2/4		XP_011513740.1
ZNF853	XM_011515439.4	c.22G>A	p.Glu8Lys	missense_variant	2/4		XP_011513741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF853	ENST00000457543.4	c.67G>A	p.Glu23Lys	missense_variant	2/3	3	NM_017560.3	ENSP00000455585.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000261 AC: 36 AN: 1380372 Hom.: 0 Cov.: 38 AF XY: 0.0000250 AC XY: 17 AN XY: 680464

Gnomad4 AFR exome AF: 0.0000331

Gnomad4 AMR exome AF: 0.0000599

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000584

Gnomad4 SAS exome AF: 0.0000256

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000262

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

Mar 12, 2024

The c.67G>A (p.E23K) alteration is located in exon 2 (coding exon 2) of the ZNF853 gene. This alteration results from a G to A substitution at nucleotide position 67, causing the glutamic acid (E) at amino acid position 23 to be replaced by a lysine (K). 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	Pathogenic	0.60
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.067	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.41	N
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.47	T
Polyphen		0.0030	B
Vest4		0.10
MVP		0.58
MPC		0.0081
GERP RS		-1.6
Varity_R		0.078
gMVP		0.18

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: rs1057462270; hg19: chr7-6656875;