NM_024671.4:c.543G>C

Variant names:

• chr16-30525597-C-G
• rs10871453
• NM_024671.4:c.543G>C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF768	NM_024671.4	MANE Select	c.543G>C	p.Glu181Asp	missense	Exon 2 of 2	NP_078947.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF768	ENST00000380412.7	TSL:1 MANE Select	c.543G>C	p.Glu181Asp	missense	Exon 2 of 2	ENSP00000369777.5
	ZNF768	ENST00000562803.1	TSL:3	c.450G>C	p.Glu150Asp	missense	Exon 2 of 2	ENSP00000456527.1

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

GnomAD2 exomes AF: 0.293 AC: 73743 AN: 251426 AF XY: 0.292

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 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

African (AFR) AF: 0.482 AC: 16154 AN: 33480

American (AMR) AF: 0.202 AC: 9046 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 8351 AN: 26132

East Asian (EAS) AF: 0.00189 AC: 75 AN: 39700

South Asian (SAS) AF: 0.186 AC: 16012 AN: 86254

European-Finnish (FIN) AF: 0.257 AC: 13738 AN: 53414

Middle Eastern (MID) AF: 0.313 AC: 1802 AN: 5766

European-Non Finnish (NFE) AF: 0.397 AC: 441202 AN: 1111996

Other (OTH) AF: 0.344 AC: 20782 AN: 60394

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

African (AFR) AF: 0.475 AC: 19701 AN: 41498

American (AMR) AF: 0.285 AC: 4360 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3470

East Asian (EAS) AF: 0.00520 AC: 27 AN: 5192

South Asian (SAS) AF: 0.157 AC: 757 AN: 4832

European-Finnish (FIN) AF: 0.267 AC: 2835 AN: 10602

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26421 AN: 67982

Other (OTH) AF: 0.333 AC: 703 AN: 2112

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 v4.9

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
MetaRNN	Benign	0.0010	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.64
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.60	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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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