chr19-2936537-G-A

Variant names:

• chr19-2936537-G-A
• rs35699176
• NM_021217.3:c.298C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP5 BA1

The NM_021217.3(ZNF77):​c.298C>T​(p.Gln100*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,601,876 control chromosomes in the GnomAD database, including 1,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.034 (118 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1613 hom.)
• Consequence: ZNF77 NM_021217.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

Genes affected

ZNF77 (HGNC:13150): (zinc finger protein 77) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative 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 -7 ACMG points.

• PP5: Variant 19-2936537-G-A is Pathogenic according to our data. Variant chr19-2936537-G-A is described in Lovd as [Pathogenic].
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF77	NM_021217.3	c.298C>T	p.Gln100*	stop_gained	Exon 3 of 4	ENST00000314531.5	NP_067040.1
ZNF77	NM_001426550.1	c.-243C>T		5_prime_UTR_variant	Exon 2 of 3		NP_001413479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF77	ENST00000314531.5	c.298C>T	p.Gln100*	stop_gained	Exon 3 of 4	1	NM_021217.3	ENSP00000319053.3

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5156 AN: 152170 Hom.: 117 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0331

GnomAD2 exomes AF: 0.0311 AC: 7408 AN: 238526 AF XY: 0.0319

Gnomad AFR exome AF: 0.0185

Gnomad AMR exome AF: 0.0149

Gnomad ASJ exome AF: 0.0556

Gnomad EAS exome AF: 0.000169

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.0457

Gnomad OTH exome AF: 0.0293

GnomAD4 exome AF: 0.0446 AC: 64582 AN: 1449588 Hom.: 1613 Cov.: 31 AF XY: 0.0437 AC XY: 31547 AN XY: 721164

Gnomad4 AFR exome AF: 0.0198 AC: 640 AN: 32402

Gnomad4 AMR exome AF: 0.0162 AC: 670 AN: 41260

Gnomad4 ASJ exome AF: 0.0588 AC: 1519 AN: 25840

Gnomad4 EAS exome AF: 0.000128 AC: 5 AN: 39214

Gnomad4 SAS exome AF: 0.0217 AC: 1811 AN: 83458

Gnomad4 FIN exome AF: 0.0149 AC: 796 AN: 53330

Gnomad4 NFE exome AF: 0.0512 AC: 56715 AN: 1108456

Gnomad4 Remaining exome AF: 0.0383 AC: 2293 AN: 59904

GnomAD4 genome AF: 0.0339 AC: 5160 AN: 152288 Hom.: 118 Cov.: 33 AF XY: 0.0319 AC XY: 2374 AN XY: 74484

Gnomad4 AFR AF: 0.0205 AC: 0.0205015 AN: 0.0205015

Gnomad4 AMR AF: 0.0223 AC: 0.0222963 AN: 0.0222963

Gnomad4 ASJ AF: 0.0553 AC: 0.0553314 AN: 0.0553314

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.0207 AC: 0.0206954 AN: 0.0206954

Gnomad4 FIN AF: 0.0153 AC: 0.0152542 AN: 0.0152542

Gnomad4 NFE AF: 0.0496 AC: 0.0496089 AN: 0.0496089

Gnomad4 OTH AF: 0.0327 AC: 0.0327324 AN: 0.0327324

Alfa AF: 0.0433 Hom.: 591

Bravo AF: 0.0330

TwinsUK AF: 0.0526 AC: 195

ALSPAC AF: 0.0464 AC: 179

ESP6500AA AF: 0.0204 AC: 90

ESP6500EA AF: 0.0437 AC: 376

ExAC AF: 0.0309 AC: 3752

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	33
DANN	Benign	0.94
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.026	N
Vest4		0.022
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=174/26	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35699176; hg19: chr19-2936535;