19-55642752-C-A

Position:

• chr19-55642752-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207115.2(ZNF580):​c.244C>A​(p.Pro82Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,533,632 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (79 hom.)
• Consequence: ZNF580 NM_207115.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.311

Genes affected

ZNF580 (HGNC:29473): (zinc finger protein 580) Enables sequence-specific double-stranded DNA binding activity. Involved in several processes, including cellular response to hydrogen peroxide; positive regulation of cell migration; and positive regulation of interleukin-8 production. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF581 (HGNC:25017): (zinc finger protein 581) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCDC106 (HGNC:30181): (coiled-coil domain containing 106) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017038584).
• BP6: Variant 19-55642752-C-A is Benign according to our data. Variant chr19-55642752-C-A is described in ClinVar as [Benign]. Clinvar id is 777510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF580	NM_207115.2	c.244C>A	p.Pro82Thr	missense_variant	2/2	ENST00000325333.10	NP_996998.1
ZNF580	NM_001163423.2	c.244C>A	p.Pro82Thr	missense_variant	2/2		NP_001156895.1
ZNF580	NM_016202.2	c.244C>A	p.Pro82Thr	missense_variant	1/1		NP_057286.1
ZNF581	XM_017026867.2	c.-19-1801C>A		intron_variant			XP_016882356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF580	ENST00000325333.10	c.244C>A	p.Pro82Thr	missense_variant	2/2	1	NM_207115.2	ENSP00000320050.4

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2498 AN: 152180 Hom.: 80 Cov.: 33

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00309 AC: 418 AN: 135136 Hom.: 5 AF XY: 0.00234 AC XY: 176 AN XY: 75200

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.00389

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000321

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000243

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00182 AC: 2517 AN: 1381340 Hom.: 79 Cov.: 36 AF XY: 0.00158 AC XY: 1079 AN XY: 681950

Gnomad4 AFR exome AF: 0.0630

Gnomad4 AMR exome AF: 0.00444

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00503

GnomAD4 genome AF: 0.0165 AC: 2509 AN: 152292 Hom.: 81 Cov.: 33 AF XY: 0.0157 AC XY: 1170 AN XY: 74472

Gnomad4 AFR AF: 0.0575

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00241 Hom.: 1

Bravo AF: 0.0189

ESP6500AA AF: 0.0360 AC: 135

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00317 AC: 356

Asia WGS AF: 0.00636 AC: 22 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T;T;.;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T;.;.;T;T
MetaRNN	Benign	0.0017	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	.;N;N;.;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.9	.;D;D;.;D
REVEL	Benign	0.085
Sift	Benign	0.18	.;T;T;.;T
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.90	.;P;P;.;P
Vest4		0.076, 0.068
MVP		0.068
MPC		1.0
ClinPred		0.022	T
GERP RS		-1.6
Varity_R		0.095
gMVP		0.29

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: rs114142434; hg19: chr19-56154118; COSMIC: COSV54401325; COSMIC: COSV54401325;