rs35699176

chr19-2936537-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PM4 PP5 BA1

The NM_021217.3(ZNF77):c.298C>T(p.Gln100Ter) 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

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM4: Stoplost variant in NM_021217.3 Downstream stopcodon found after 7 codons.
• 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/exons	MANE	UniProt
ZNF77	NM_021217.3	c.298C>T	p.Gln100Ter	stop_gained	3/4	ENST00000314531.5
ZNF77	XM_047439170.1	c.202C>T	p.Gln68Ter	stop_gained	3/4
ZNF77	XM_017027081.2	c.-243C>T		5_prime_UTR_variant	2/3
ZNF77	XM_047439171.1	c.-243C>T		5_prime_UTR_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF77	ENST00000314531.5	c.298C>T	p.Gln100Ter	stop_gained	3/4	1	NM_021217.3	P1

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

GnomAD3 exomes AF: 0.0311 AC: 7408 AN: 238526 Hom.: 164 AF XY: 0.0319 AC XY: 4129 AN XY: 129358

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 SAS exome AF: 0.0225

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

Gnomad4 AMR exome AF: 0.0162

Gnomad4 ASJ exome AF: 0.0588

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.0217

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0512

Gnomad4 OTH exome AF: 0.0383

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

Gnomad4 AMR AF: 0.0223

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0496

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0442 Hom.: 297

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
MutationTaster	Benign	1.0	D
Vest4		0.022
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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;