7-64069010-C-G

Position:

• chr7-64069010-C-G

Variant summary

Our verdict is Likely benign. Variant got -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. 12/18 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

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]

ZNF727 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF727	NM_001159522.3	c.123C>G	p.Phe41Leu	missense_variant	2/4	ENST00000456806.3	NP_001152994.1
ZNF727	XM_017012225.3	c.123C>G	p.Phe41Leu	missense_variant	2/3		XP_016867714.1
ZNF727	XR_242241.4	n.311C>G		non_coding_transcript_exon_variant	2/5
ZNF727	XR_927469.2	n.311C>G		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF727	ENST00000456806.3	c.123C>G	p.Phe41Leu	missense_variant	2/4	4	NM_001159522.3	ENSP00000485448.1
ENSG00000285544	ENST00000647787.1	n.196+23386C>G		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jan 24, 2024

The c.123C>G (p.F41L) alteration is located in exon 2 (coding exon 2) of the ZNF727 gene. This alteration results from a C to G substitution at nucleotide position 123, causing the phenylalanine (F) at amino acid position 41 to be replaced by a leucine (L). 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	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
MutationTaster	Benign	1.0	D
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

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: chr7-63529388;