chr19-57841386-C-G

Position:

• chr19-57841386-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001376223.1(ZNF587B):​c.712C>G​(p.Arg238Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,585,848 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (32 hom.)
• Consequence: ZNF587B NM_001376223.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.840

Genes affected

ZNF587B (HGNC:37142): (zinc finger protein 587B) 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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026150942).
• BP6: Variant 19-57841386-C-G is Benign according to our data. Variant chr19-57841386-C-G is described in ClinVar as [Benign]. Clinvar id is 781537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1789/152156) while in subpopulation AFR AF= 0.0412 (1712/41520). AF 95% confidence interval is 0.0396. There are 33 homozygotes in gnomad4. There are 799 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF587B	NM_001376223.1	c.712C>G	p.Arg238Gly	missense_variant	3/3	ENST00000594901.2	NP_001363152.1
ZNF587B	NM_001204818.2	c.712C>G	p.Arg238Gly	missense_variant	3/4		NP_001191747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF587B	ENST00000594901.2	c.712C>G	p.Arg238Gly	missense_variant	3/3	4	NM_001376223.1	ENSP00000469623	P4
ZNF587B	ENST00000651253.2	c.709C>G	p.Arg237Gly	missense_variant	3/3			ENSP00000499083	A2
ZNF587B	ENST00000594328.1	c.562C>G	p.Arg188Gly	missense_variant	4/4	2		ENSP00000472004
ZNF587B	ENST00000442832.8	c.712C>G	p.Arg238Gly	missense_variant	3/4	2		ENSP00000392410

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1782 AN: 152038 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00301 AC: 614 AN: 203962 Hom.: 15 AF XY: 0.00225 AC XY: 247 AN XY: 109810

Gnomad AFR exome AF: 0.0455

Gnomad AMR exome AF: 0.00190

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000683

Gnomad SAS exome AF: 0.0000369

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000103

Gnomad OTH exome AF: 0.000756

GnomAD4 exome AF: 0.00110 AC: 1579 AN: 1433692 Hom.: 32 Cov.: 35 AF XY: 0.000941 AC XY: 669 AN XY: 710852

Gnomad4 AFR exome AF: 0.0414

Gnomad4 AMR exome AF: 0.00198

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000718

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000246

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.0118 AC: 1789 AN: 152156 Hom.: 33 Cov.: 33 AF XY: 0.0107 AC XY: 799 AN XY: 74402

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.00367

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.000508 Hom.: 0

Bravo AF: 0.0132

ExAC AF: 0.00334 AC: 403

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	Feb 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.062
DANN	Benign	0.60
DEOGEN2	Benign	0.0024	T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.0090	T;T;T
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.8	.;N;.
PROVEAN	Uncertain	-3.6	.;D;.
REVEL	Benign	0.013
Sift	Benign	0.35	.;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.010	.;B;.
Vest4		0.12, 0.29
MVP		0.055
MPC		0.44
ClinPred		0.0064	T
GERP RS		-4.7
Varity_R		0.099
gMVP		0.020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs113335262; hg19: chr19-58352754;