7-64068911-T-A

Position:

• chr7-64068911-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001159522.3(ZNF727):​c.24T>A​(p.Asp8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,449,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ZNF727 NM_001159522.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.173

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF727	NM_001159522.3	c.24T>A	p.Asp8Glu	missense_variant	2/4	ENST00000456806.3	NP_001152994.1
ZNF727	XM_017012225.3	c.24T>A	p.Asp8Glu	missense_variant	2/3		XP_016867714.1
ZNF727	XR_242241.4	n.212T>A		non_coding_transcript_exon_variant	2/5
ZNF727	XR_927469.2	n.212T>A		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF727	ENST00000456806.3	c.24T>A	p.Asp8Glu	missense_variant	2/4	4	NM_001159522.3	ENSP00000485448.1
ENSG00000285544	ENST00000647787.1	n.196+23287T>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000131 AC: 19 AN: 1449256 Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9 AN XY: 720206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000163

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

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

Nov 11, 2024

The c.24T>A (p.D8E) alteration is located in exon 2 (coding exon 2) of the ZNF727 gene. This alteration results from a T to A substitution at nucleotide position 24, causing the aspartic acid (D) at amino acid position 8 to be replaced by a glutamic acid (E). 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	0.46
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0028	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Benign	0.31	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.13
MutPred		0.81		Loss of loop (P = 0.0986);
MVP		0.12
ClinPred		0.78	D
GERP RS		0.15
Varity_R		0.058
gMVP		0.045

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

LitVar

Other links and lift over

dbSNP: rs1789913836; hg19: chr7-63529289;