19-57908853-A-G

Variant names:

• chr19-57908853-A-G
• rs116338997
• NM_152475.3:c.1425T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_152475.3(ZNF417):​c.1425T>C​(p.Asn475Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,613,584 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (41 hom.)
• Consequence: ZNF417 NM_152475.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -8.83

Genes affected

ZNF417 (HGNC:20646): (zinc finger protein 417) 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]

ENSG00000269476 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-57908853-A-G is Benign according to our data. Variant chr19-57908853-A-G is described in ClinVar as [Benign]. Clinvar id is 774743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.83 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2034/151708) while in subpopulation AFR AF= 0.0464 (1919/41330). AF 95% confidence interval is 0.0447. There are 53 homozygotes in gnomad4. There are 935 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF417	NM_152475.3	c.1425T>C	p.Asn475Asn	synonymous_variant	Exon 3 of 3	ENST00000312026.6	NP_689688.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF417	ENST00000312026.6	c.1425T>C	p.Asn475Asn	synonymous_variant	Exon 3 of 3	1	NM_152475.3	ENSP00000311319.4
ZNF417	ENST00000595559.1	c.1422T>C	p.Asn474Asn	synonymous_variant	Exon 3 of 3	1		ENSP00000472272.1
ENSG00000269476	ENST00000602124.1	n.34+3207T>C		intron_variant	Intron 3 of 5	3		ENSP00000470782.1
ZNF417	ENST00000594396.1	c.106+3207T>C		intron_variant	Intron 1 of 2	3		ENSP00000472352.1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2036 AN: 151590 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00539

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00870

GnomAD3 exomes AF: 0.00341 AC: 858 AN: 251446 Hom.: 10 AF XY: 0.00247 AC XY: 335 AN XY: 135892

Gnomad AFR exome AF: 0.0460

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00140 AC: 2053 AN: 1461876 Hom.: 41 Cov.: 81 AF XY: 0.00123 AC XY: 892 AN XY: 727238

Gnomad4 AFR exome AF: 0.0470

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.0134 AC: 2034 AN: 151708 Hom.: 53 Cov.: 32 AF XY: 0.0126 AC XY: 935 AN XY: 74158

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.00538

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00860

Alfa AF: 0.000892 Hom.: 0

Bravo AF: 0.0155

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.98
DANN	Benign	0.36

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: rs116338997; hg19: chr19-58420221;