7-64077857-G-C

Position:

• chr7-64077857-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001159522.3(ZNF727):​c.808G>C​(p.Asp270His) 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: 33)
• Consequence: ZNF727 NM_001159522.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.37

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]

ENSG00000285544 (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=0.05775538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF727	NM_001159522.3	c.808G>C	p.Asp270His	missense_variant	4/4	ENST00000456806.3	NP_001152994.1
ZNF727	XM_017012225.3	c.712G>C	p.Asp238His	missense_variant	3/3		XP_016867714.1
ZNF727	XR_242241.4	n.996G>C		non_coding_transcript_exon_variant	4/5
ZNF727	XR_927469.2	n.996G>C		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF727	ENST00000456806.3	c.808G>C	p.Asp270His	missense_variant	4/4	4	NM_001159522.3	ENSP00000485448.1
ENSG00000285544	ENST00000647787.1	n.197-17656G>C		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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

Mar 14, 2023

The c.808G>C (p.D270H) alteration is located in exon 4 (coding exon 4) of the ZNF727 gene. This alteration results from a G to C substitution at nucleotide position 808, causing the aspartic acid (D) at amino acid position 270 to be replaced by a histidine (H). 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	Pathogenic	0.78
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Benign	0.38
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00014	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.23	N
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.47	T
Polyphen		0.99	D
Vest4		0.054
MutPred		0.27		Gain of catalytic residue at D270 (P = 0.0179);
MVP		0.014
ClinPred		0.13	T
GERP RS		-2.0
Varity_R		0.053
gMVP		0.037

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: chr7-63538235;