15-90360079-A-G

Position:

• chr15-90360079-A-G

Variant summary

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

The NM_001004309.3(ZNF774):​c.248A>G​(p.Asn83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,613,200 control chromosomes in the GnomAD database, including 216,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.58 (26837 hom., cov: 32)
  • Exomes 𝑓: 0.50 (189406 hom.)
• Consequence: ZNF774 NM_001004309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

Genes affected

ZNF774 (HGNC:33108): (zinc finger protein 774) Predicted to enable DNA-binding transcription factor 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. Predicted to be active 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=9.990085E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF774	NM_001004309.3	c.248A>G	p.Asn83Ser	missense_variant	4/4	ENST00000354377.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF774	ENST00000354377.8	c.248A>G	p.Asn83Ser	missense_variant	4/4	1	NM_001004309.3	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87720 AN: 151940 Hom.: 26796 Cov.: 32

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.557

GnomAD3 exomes AF: 0.562 AC: 141104 AN: 250992 Hom.: 41928 AF XY: 0.552 AC XY: 74946 AN XY: 135678

Gnomad AFR exome AF: 0.750

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.858

Gnomad SAS exome AF: 0.598

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.472

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.502 AC: 733088 AN: 1461142 Hom.: 189406 Cov.: 42 AF XY: 0.502 AC XY: 365155 AN XY: 726840

Gnomad4 AFR exome AF: 0.756

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.845

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.578 AC: 87816 AN: 152058 Hom.: 26837 Cov.: 32 AF XY: 0.577 AC XY: 42887 AN XY: 74312

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.556

Alfa AF: 0.501 Hom.: 34800

Bravo AF: 0.602

TwinsUK AF: 0.456 AC: 1692

ALSPAC AF: 0.483 AC: 1863

ESP6500AA AF: 0.746 AC: 3280

ESP6500EA AF: 0.475 AC: 4079

ExAC AF: 0.560 AC: 68048

Asia WGS AF: 0.692 AC: 2408 AN: 3478

EpiCase AF: 0.471

EpiControl AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.60
DEOGEN2	Benign	0.00013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.017
Sift	Benign	0.60	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.0050
MPC		0.036
ClinPred		0.0041	T
GERP RS		1.7
Varity_R		0.032
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2589957; hg19: chr15-90903311;