7-64069010-C-G

Variant names:

• chr7-64069010-C-G
• NM_001159522.3:c.123C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001159522.3(ZNF727):​c.123C>G​(p.Phe41Leu) 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: 32)
• Consequence: ZNF727 NM_001159522.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.480
• Publications: 0 publications found

Genes affected

ZNF727 (HGNC:22785): (zinc finger protein 727) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060265183).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159522.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF727	NM_001159522.3	MANE Select	c.123C>G	p.Phe41Leu	missense	Exon 2 of 4	NP_001152994.1	A8MUV8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF727	ENST00000456806.3	TSL:4 MANE Select	c.123C>G	p.Phe41Leu	missense	Exon 2 of 4	ENSP00000485448.1	A8MUV8
	ZNF727	ENST00000889951.1		c.123C>G	p.Phe41Leu	missense	Exon 2 of 4	ENSP00000560010.1
	ZNF727	ENST00000889950.1		c.123C>G	p.Phe41Leu	missense	Exon 2 of 3	ENSP00000560009.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.78	N
PhyloP100		-0.48
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.17	T
Polyphen		0.026	B
Vest4		0.024
MutPred		0.62		Loss of catalytic residue at F41 (P = 0.0083)
MVP		0.014
ClinPred		0.87	D
GERP RS		0.15
Varity_R		0.086
gMVP		0.023
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr7-63529388;