7-149071265-G-T

Position:

• chr7-149071265-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152411.4(ZNF786):​c.1507C>A​(p.His503Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF786 NM_152411.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.30

Genes affected

ZNF786 (HGNC:21806): (zinc finger protein 786) Predicted to enable DNA-binding transcription activator 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 by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF786	NM_152411.4	c.1507C>A	p.His503Asn	missense_variant	4/4	ENST00000491431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF786	ENST00000491431.2	c.1507C>A	p.His503Asn	missense_variant	4/4	1	NM_152411.4	P1
ZNF786	ENST00000316286.13	c.1249C>A	p.His417Asn	missense_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248468 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135040

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000826 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

Oct 22, 2021

The c.1507C>A (p.H503N) alteration is located in exon 4 (coding exon 4) of the ZNF786 gene. This alteration results from a C to A substitution at nucleotide position 1507, causing the histidine (H) at amino acid position 503 to be replaced by an asparagine (N). 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	0.84
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Benign	0.97
Eigen	Benign	0.17
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Uncertain	0.23	D
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.8	D;D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.52
MutPred		0.69		.;Gain of methylation at R502 (P = 0.0909);
MVP		0.52
MPC		0.35
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.52
gMVP		0.17

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: rs772353386; hg19: chr7-148768357;