chr19-37565472-C-T

Position:

• chr19-37565472-C-T

Variant summary

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

The NM_016536.5(ZNF571):​c.956G>A​(p.Gly319Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,611,920 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (130 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (93 hom.)
• Consequence: ZNF571 NM_016536.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.76

Genes affected

ZNF571 (HGNC:25000): (zinc finger protein 571) 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. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF571-AS1 (HGNC:44324): (ZNF571 antisense RNA 1)

ZNF540 (HGNC:25331): (zinc finger protein 540) Enables translation repressor activity, mRNA regulatory element binding. Involved in negative regulation of transcription, DNA-templated and negative regulation of translation. 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=0.0031697154).
• BP6: Variant 19-37565472-C-T is Benign according to our data. Variant chr19-37565472-C-T is described in ClinVar as [Benign]. Clinvar id is 787491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF571	NM_016536.5	c.956G>A	p.Gly319Asp	missense_variant	4/4	ENST00000451802.7
ZNF571-AS1	NR_038248.1	n.338-559C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF571	ENST00000451802.7	c.956G>A	p.Gly319Asp	missense_variant	4/4	1	NM_016536.5	P1
ZNF571-AS1	ENST00000585578.5	n.210-559C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3302 AN: 150914 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00671

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0173

GnomAD3 exomes AF: 0.00601 AC: 1499 AN: 249540 Hom.: 64 AF XY: 0.00445 AC XY: 600 AN XY: 134908

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.00516

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00218 AC: 3190 AN: 1460884 Hom.: 93 Cov.: 35 AF XY: 0.00187 AC XY: 1362 AN XY: 726712

Gnomad4 AFR exome AF: 0.0761

Gnomad4 AMR exome AF: 0.00570

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000765

Gnomad4 OTH exome AF: 0.00466

GnomAD4 genome AF: 0.0219 AC: 3305 AN: 151036 Hom.: 130 Cov.: 32 AF XY: 0.0214 AC XY: 1578 AN XY: 73792

Gnomad4 AFR AF: 0.0754

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0109 Hom.: 26

Bravo AF: 0.0251

ESP6500AA AF: 0.0769 AC: 339

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00725 AC: 880

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

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	Aug 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.0095	T;T;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.000030	N
LIST_S2	Benign	0.28	T;.;.;.
MetaRNN	Benign	0.0032	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.30	N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N;.;N;N
REVEL	Benign	0.032
Sift	Benign	0.22	T;.;T;T
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.79	P;P;P;P
Vest4		0.24
MVP		0.18
MPC		0.25
ClinPred		0.031	T
GERP RS		-0.015
Varity_R		0.064
gMVP		0.029

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: rs61744939; hg19: chr19-38056374;