16-30534673-C-G

Position:

• chr16-30534673-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001305018.2(ZNF747):​c.7G>C​(p.Asp3His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000432 in 1,388,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ZNF747 NM_001305018.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0640

Genes affected

ZNF747 (HGNC:28350): (zinc finger protein 747) Predicted to enable metal ion binding activity. Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10636005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF747	NM_001305018.2	c.7G>C	p.Asp3His	missense_variant	1/3	ENST00000693075.1	NP_001291947.1
ZNF747	NM_001305019.2	c.7G>C	p.Asp3His	missense_variant	1/3		NP_001291948.1
ZNF747	NM_023931.4	c.7G>C	p.Asp3His	missense_variant	1/2		NP_076420.1
ZNF747	NM_001305020.2	c.7G>C	p.Asp3His	missense_variant	1/2		NP_001291949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF747	ENST00000693075.1	c.7G>C	p.Asp3His	missense_variant	1/3		NM_001305018.2	ENSP00000509633	A2
ZNF747	ENST00000252799.3	c.7G>C	p.Asp3His	missense_variant	1/2	1		ENSP00000252799
ZNF747	ENST00000395094.3	c.7G>C	p.Asp3His	missense_variant	1/2	1		ENSP00000378528
ZNF747	ENST00000568028.1	c.7G>C	p.Asp3His	missense_variant	1/3	2		ENSP00000457274	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000432 AC: 6 AN: 1388726 Hom.: 0 Cov.: 31 AF XY: 0.00000437 AC XY: 3 AN XY: 685838

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000820

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000345

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000891 AC: 1

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

Dec 21, 2022

The c.7G>C (p.D3H) alteration is located in exon 1 (coding exon 1) of the ZNF747 gene. This alteration results from a G to C substitution at nucleotide position 7, causing the aspartic acid (D) at amino acid position 3 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	Benign	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	.;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.32	T;T;.
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.94	N;N;N
REVEL	Benign	0.067
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.10
MutPred		0.26		Loss of phosphorylation at S5 (P = 0.1209);Loss of phosphorylation at S5 (P = 0.1209);Loss of phosphorylation at S5 (P = 0.1209);
MVP		0.092
MPC		0.89
ClinPred		0.50	T
GERP RS		1.5
Varity_R		0.088
gMVP		0.36

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: rs749526208; hg19: chr16-30545994;