7-6621923-C-A

Position:

• chr7-6621923-C-A

Variant summary

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

The NM_017560.3(ZNF853):​c.932C>A​(p.Pro311His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,398,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: ZNF853 NM_017560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.933

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 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=0.17578244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF853	NM_017560.3	c.932C>A	p.Pro311His	missense_variant	3/3	ENST00000457543.4	NP_060030.1
ZNF853	NM_001353546.2	c.887C>A	p.Pro296His	missense_variant	3/3		NP_001340475.1
ZNF853	XM_011515438.4	c.1010C>A	p.Pro337His	missense_variant	4/4		XP_011513740.1
ZNF853	XM_011515439.4	c.965C>A	p.Pro322His	missense_variant	4/4		XP_011513741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF853	ENST00000457543.4	c.932C>A	p.Pro311His	missense_variant	3/3	3	NM_017560.3	ENSP00000455585.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000257 AC: 36 AN: 1398838 Hom.: 0 Cov.: 33 AF XY: 0.0000217 AC XY: 15 AN XY: 689914

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: 0.0000324

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

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

Nov 18, 2022

The c.932C>A (p.P311H) alteration is located in exon 3 (coding exon 3) of the ZNF853 gene. This alteration results from a C to A substitution at nucleotide position 932, causing the proline (P) at amino acid position 311 to be replaced by a histidine (H). 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	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.78
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.18	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	N
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.24
MVP		0.29
MPC		0.0080
GERP RS		0.34
Varity_R		0.19
gMVP		0.098

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: rs1157351541; hg19: chr7-6661554; COSMIC: COSV105940501;