7-6621236-C-T

Position:

• chr7-6621236-C-T

Variant summary

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

The NM_017560.3(ZNF853):​c.245C>T​(p.Thr82Ile) 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)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF853 NM_017560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.238

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=0.07278049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF853	NM_017560.3	c.245C>T	p.Thr82Ile	missense_variant	3/3	ENST00000457543.4	NP_060030.1
ZNF853	NM_001353546.2	c.200C>T	p.Thr67Ile	missense_variant	3/3		NP_001340475.1
ZNF853	XM_011515438.4	c.323C>T	p.Thr108Ile	missense_variant	4/4		XP_011513740.1
ZNF853	XM_011515439.4	c.278C>T	p.Thr93Ile	missense_variant	4/4		XP_011513741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF853	ENST00000457543.4	c.245C>T	p.Thr82Ile	missense_variant	3/3	3	NM_017560.3	ENSP00000455585.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.17e-7 AC: 1 AN: 1394528 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 687240

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: 9.29e-7

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

Aug 21, 2023

The c.245C>T (p.T82I) alteration is located in exon 3 (coding exon 3) of the ZNF853 gene. This alteration results from a C to T substitution at nucleotide position 245, causing the threonine (T) at amino acid position 82 to be replaced by an isoleucine (I). 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	0.33
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.65
DEOGEN2	Benign	0.017	T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.073	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.48	N
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.094	T
Polyphen		0.15	B
Vest4		0.080
MVP		0.40
MPC		0.0081
GERP RS		2.8
Varity_R		0.054
gMVP		0.090

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: chr7-6660867;