7-149432104-T-G

Position:

• chr7-149432104-T-G

Variant summary

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

The NM_015694.3(ZNF777):​c.2168A>C​(p.Lys723Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 34)
  • Failed GnomAD Quality Control
• Consequence: ZNF777 NM_015694.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.828

Genes affected

ZNF777 (HGNC:22213): (zinc finger protein 777) 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. Predicted to be active in nucleus. [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=0.23731008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF777	NM_015694.3	c.2168A>C	p.Lys723Thr	missense_variant	6/6	ENST00000247930.5	NP_056509.2
ZNF777	XM_005249980.4	c.2300A>C	p.Lys767Thr	missense_variant	6/6		XP_005250037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF777	ENST00000247930.5	c.2168A>C	p.Lys723Thr	missense_variant	6/6	1	NM_015694.3	ENSP00000247930	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 147008 Hom.: 0 Cov.: 34 FAILED QC

Gnomad AFR AF: 0.0000253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000680 AC: 1 AN: 147008 Hom.: 0 Cov.: 34 AF XY: 0.0000139 AC XY: 1 AN XY: 71704

Gnomad4 AFR AF: 0.0000253

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

May 16, 2023

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.67	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.11
Sift	Benign	0.065	T
Sift4G	Uncertain	0.026	D
Polyphen		0.99	D
Vest4		0.22
MutPred		0.43		Loss of methylation at K723 (P = 0);
MVP		0.24
MPC		3.1
ClinPred		0.73	D
GERP RS		4.5
gMVP		0.85

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: rs1799318408; hg19: chr7-149129195;