2-179769508-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152520.6(ZNF385B):c.293G>T(p.Ser98Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00477 in 1,613,766 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (40 hom.)
• Consequence: ZNF385B NM_152520.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.66

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074246526).
• BP6: Variant 2-179769508-C-A is Benign according to our data. Variant chr2-179769508-C-A is described in ClinVar as [Benign]. Clinvar id is 720664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385B	NM_152520.6	c.293G>T	p.Ser98Ile	missense_variant	3/10	ENST00000410066.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385B	ENST00000410066.7	c.293G>T	p.Ser98Ile	missense_variant	3/10	1	NM_152520.6	P1
ZNF385B	ENST00000451732.6			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 514 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00531

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00389 AC: 972 AN: 250078 Hom.: 9 AF XY: 0.00447 AC XY: 605 AN XY: 135290

Gnomad AFR exome AF: 0.000617

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0103

Gnomad FIN exome AF: 0.00144

Gnomad NFE exome AF: 0.00474

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00491 AC: 7182 AN: 1461450 Hom.: 40 Cov.: 32 AF XY: 0.00507 AC XY: 3689 AN XY: 727028

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0106

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.00522

Gnomad4 OTH exome AF: 0.00398

GnomAD4 genome AF: 0.00337 AC: 514 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.00318 AC XY: 237 AN XY: 74484

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00531

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00511 Hom.: 2

Bravo AF: 0.00376

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00535 AC: 46

ExAC AF: 0.00415 AC: 504

Asia WGS AF: 0.00202 AC: 7 AN: 3478

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_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	22
Dann	Uncertain	0.98
Eigen	Benign	0.080
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.0074	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.86	D
PrimateAI	Uncertain	0.49	T
REVEL	Benign	0.14
Polyphen		0.38	.;B
MVP		0.38
MPC		0.28
ClinPred		0.022	T
GERP RS		6.1
Varity_R		0.13
gMVP		0.33

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: rs148987445; hg19: chr2-180634235;