7-6621313-C-G

Position:

• chr7-6621313-C-G

Variant summary

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

The NM_017560.3(ZNF853):​c.322C>G​(p.Gln108Glu) 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. 13/19 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)
• Consequence: ZNF853 NM_017560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.989

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=0.055215716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF853	NM_017560.3	c.322C>G	p.Gln108Glu	missense_variant	3/3	ENST00000457543.4	NP_060030.1
ZNF853	NM_001353546.2	c.277C>G	p.Gln93Glu	missense_variant	3/3		NP_001340475.1
ZNF853	XM_011515438.4	c.400C>G	p.Gln134Glu	missense_variant	4/4		XP_011513740.1
ZNF853	XM_011515439.4	c.355C>G	p.Gln119Glu	missense_variant	4/4		XP_011513741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF853	ENST00000457543.4	c.322C>G	p.Gln108Glu	missense_variant	3/3	3	NM_017560.3	ENSP00000455585.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Jan 18, 2022

The c.322C>G (p.Q108E) alteration is located in exon 3 (coding exon 3) of the ZNF853 gene. This alteration results from a C to G substitution at nucleotide position 322, causing the glutamine (Q) at amino acid position 108 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.45
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.055	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.49	N
Sift	Benign	0.22	T
Sift4G	Benign	0.092	T
Polyphen		0.0010	B
Vest4		0.097
MVP		0.38
MPC		0.0081
GERP RS		0.85
Varity_R		0.051
gMVP		0.043

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: chr7-6660944;