7-64077672-C-A

Variant names:

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

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>A​(p.Ala208Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A208V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF727 NM_001159522.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.14571986).

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>A	p.Ala208Asp	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>A	p.Ala208Asp	missense	Exon 4 of 4	ENSP00000485448.1	A8MUV8
	ZNF727	ENST00000889951.1		c.599C>A	p.Ala200Asp	missense	Exon 4 of 4	ENSP00000560010.1
	ZNF727	ENST00000889950.1		c.527C>A	p.Ala176Asp	missense	Exon 3 of 3	ENSP00000560009.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407586 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 695172

African (AFR) AF: 0.00 AC: 0 AN: 31760

American (AMR) AF: 0.00 AC: 0 AN: 36432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25286

East Asian (EAS) AF: 0.00 AC: 0 AN: 36238

South Asian (SAS) AF: 0.00 AC: 0 AN: 79982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083766

Other (OTH) AF: 0.0000171 AC: 1 AN: 58444

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.54
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00015	N
LIST_S2	Benign	0.087	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.57
PrimateAI	Benign	0.26	T
Sift4G	Uncertain	0.015	D
Polyphen		0.95	P
Vest4		0.16
MutPred		0.59		Gain of ubiquitination at K211 (P = 0.0396)
MVP		0.085
ClinPred		0.34	T
GERP RS		-0.11
Varity_R		0.092
gMVP		0.025
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;