rs2014572

Variant names:

• chr19-57248650-G-A
• rs2014572
• NM_001023563.4:c.203G>A

Variant summary

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

The NM_001023563.4(ZNF805):​c.203G>A​(p.Gly68Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,596,036 control chromosomes in the GnomAD database, including 197,680 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.44 (15817 hom., cov: 32)
  • Exomes 𝑓: 0.50 (181863 hom.)
• Consequence: ZNF805 NM_001023563.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604

Genes affected

ZNF805 (HGNC:23272): (zinc finger protein 805) 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=2.3294138E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF805	NM_001023563.4	c.203G>A	p.Gly68Glu	missense_variant	Exon 3 of 4	ENST00000414468.3	NP_001018857.2
ZNF805	NM_001145078.2	c.-197G>A		5_prime_UTR_variant	Exon 2 of 3		NP_001138550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF805	ENST00000414468.3	c.203G>A	p.Gly68Glu	missense_variant	Exon 3 of 4	5	NM_001023563.4	ENSP00000412999.1
ZNF805	ENST00000354309	c.-197G>A		5_prime_UTR_variant	Exon 2 of 3	5		ENSP00000365414.2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66649 AN: 151944 Hom.: 15820 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.457

GnomAD3 exomes AF: 0.464 AC: 106374 AN: 229304 Hom.: 25990 AF XY: 0.473 AC XY: 58106 AN XY: 122970

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.162

Gnomad SAS exome AF: 0.489

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.496 AC: 716218 AN: 1443974 Hom.: 181863 Cov.: 48 AF XY: 0.498 AC XY: 356897 AN XY: 716512

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome AF: 0.438 AC: 66646 AN: 152062 Hom.: 15817 Cov.: 32 AF XY: 0.440 AC XY: 32682 AN XY: 74312

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.459

Alfa AF: 0.495 Hom.: 14455

Bravo AF: 0.421

TwinsUK AF: 0.514 AC: 1907

ALSPAC AF: 0.513 AC: 1979

ESP6500AA AF: 0.276 AC: 382

ESP6500EA AF: 0.518 AC: 1648

ExAC AF: 0.446 AC: 53940

Asia WGS AF: 0.324 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.77
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.000023	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.83	L
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.10
Sift	Benign	0.085	T
Sift4G	Benign	0.14	T
Polyphen		0.68	P
Vest4		0.049
MPC		0.40
ClinPred		0.036	T
GERP RS		-0.0036
Varity_R		0.14
gMVP		0.055

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2014572; hg19: chr19-57760018; COSMIC: COSV62832081;