2-179769594-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_152520.6(ZNF385B):c.207C>T(p.Asn69=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,614,136 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (25 hom.)
• Consequence: ZNF385B NM_152520.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.525

Genes affected

ZNF385B (HGNC:26332): (zinc finger protein 385B) Enables p53 binding activity. Involved in intrinsic apoptotic signaling pathway by p53 class mediator. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-179769594-G-A is Benign according to our data. Variant chr2-179769594-G-A is described in ClinVar as [Benign]. Clinvar id is 774598.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.525 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385B	NM_152520.6	c.207C>T	p.Asn69=	synonymous_variant	3/10	ENST00000410066.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385B	ENST00000410066.7	c.207C>T	p.Asn69=	synonymous_variant	3/10	1	NM_152520.6	P1
ZNF385B	ENST00000451732.6	c.207C>T	p.Asn69=	synonymous_variant	3/3	4

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 698 AN: 152130 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00639

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00388 AC: 975 AN: 251406 Hom.: 6 AF XY: 0.00400 AC XY: 543 AN XY: 135890

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00640

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00581 AC: 8494 AN: 1461888 Hom.: 25 Cov.: 32 AF XY: 0.00565 AC XY: 4112 AN XY: 727244

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.00358

Gnomad4 ASJ exome AF: 0.00390

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000684

Gnomad4 FIN exome AF: 0.00103

Gnomad4 NFE exome AF: 0.00692

Gnomad4 OTH exome AF: 0.00550

GnomAD4 genome AF: 0.00459 AC: 699 AN: 152248 Hom.: 6 Cov.: 32 AF XY: 0.00466 AC XY: 347 AN XY: 74456

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00641

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00528 Hom.: 1

Bravo AF: 0.00530

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00823

EpiControl AF: 0.00865

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.32
Dann	Benign	0.74

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: rs61744327; hg19: chr2-180634321; COSMIC: COSV69800747; COSMIC: COSV69800747;