NM_001159522.3:c.623C>T

Variant names:

• chr7-64077672-C-T
• rs1352940568
• NM_001159522.3:c.623C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001159522.3(ZNF727):​c.623C>T​(p.Ala208Val) 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. 14/19 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: ZNF727 NM_001159522.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.567
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08439931).

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.623C>T	p.Ala208Val	missense	Exon 4 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.623C>T	p.Ala208Val	missense	Exon 4 of 4	ENSP00000485448.1	A8MUV8
	ZNF727	ENST00000889951.1		c.599C>T	p.Ala200Val	missense	Exon 4 of 4	ENSP00000560010.1
	ZNF727	ENST00000889950.1		c.527C>T	p.Ala176Val	missense	Exon 3 of 3	ENSP00000560009.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.2
DANN	Benign	0.74
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00023	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.57
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.13	T
Polyphen		0.73	P
Vest4		0.096
MutPred		0.54		Loss of ubiquitination at K207 (P = 0.0648)
MVP		0.014
ClinPred		0.14	T
GERP RS		-0.11
Varity_R		0.021
gMVP		0.0080
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

dbSNP: rs1352940568; hg19: chr7-63538050;