16-30525597-C-G

Position:

• chr16-30525597-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024671.4(ZNF768):​c.543G>C​(p.Glu181Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,614,046 control chromosomes in the GnomAD database, including 113,212 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (11398 hom., cov: 33)
  • Exomes 𝑓: 0.36 (101814 hom.)
• Consequence: ZNF768 NM_024671.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

Genes affected

ZNF768 (HGNC:26273): (zinc finger protein 768) Enables RNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010181665).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF768	NM_024671.4	c.543G>C	p.Glu181Asp	missense_variant	2/2	ENST00000380412.7	NP_078947.3
ZNF768	XM_017023665.3	c.615G>C	p.Glu205Asp	missense_variant	2/2		XP_016879154.1
ZNF768	XM_017023666.2	c.450G>C	p.Glu150Asp	missense_variant	2/2		XP_016879155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF768	ENST00000380412.7	c.543G>C	p.Glu181Asp	missense_variant	2/2	1	NM_024671.4	ENSP00000369777	P2
ZNF768	ENST00000562803.1	c.450G>C	p.Glu150Asp	missense_variant	2/2	3		ENSP00000456527	A2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56443 AN: 152068 Hom.: 11399 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.336

GnomAD3 exomes AF: 0.293 AC: 73743 AN: 251426 Hom.: 12952 AF XY: 0.292 AC XY: 39745 AN XY: 135892

Gnomad AFR exome AF: 0.477

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.00348

Gnomad SAS exome AF: 0.180

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.361 AC: 527162 AN: 1461860 Hom.: 101814 Cov.: 71 AF XY: 0.355 AC XY: 258286 AN XY: 727230

Gnomad4 AFR exome AF: 0.482

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.00189

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.371 AC: 56458 AN: 152186 Hom.: 11398 Cov.: 33 AF XY: 0.359 AC XY: 26746 AN XY: 74404

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.333

Alfa AF: 0.375 Hom.: 3665

Bravo AF: 0.378

TwinsUK AF: 0.407 AC: 1510

ALSPAC AF: 0.405 AC: 1560

ESP6500AA AF: 0.461 AC: 2024

ESP6500EA AF: 0.389 AC: 3348

ExAC AF: 0.299 AC: 36357

Asia WGS AF: 0.118 AC: 411 AN: 3478

EpiCase AF: 0.374

EpiControl AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0088	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.56	T;T
MetaRNN	Benign	0.0010	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	0.86	P;P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.50	N;.
REVEL	Benign	0.12
Sift	Benign	0.10	T;.
Sift4G	Benign	0.60	T;T
Polyphen		0.96	D;.
Vest4		0.35
MutPred		0.076		Loss of methylation at K183 (P = 0.0996);.;
MPC		0.98
ClinPred		0.017	T
GERP RS		0.64
Varity_R		0.084
gMVP		0.19

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: rs10871453; hg19: chr16-30536918; COSMIC: COSV53224238; COSMIC: COSV53224238;