Variant 3-21564601-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024697.3(ZNF385D):c.249C>A(p.Asn83Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000957 in 1,557,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ZNF385D
NM_024697.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.34

Variant links:

Genes affected

ZNF385D (HGNC:26191): (zinc finger protein 385D) Enables sequence-specific double-stranded DNA binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF385D links:

ZNF385D-AS1 (HGNC:41136): (ZNF385D antisense RNA 1)

ZNF385D-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385D	NM_024697.3 linkuse as main transcript	c.249C>A	p.Asn83Lys	missense_variant	3/8	ENST00000281523.8
ZNF385D-AS1	NR_046731.1 linkuse as main transcript	n.208-14588G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385D	ENST00000281523.8 linkuse as main transcript	c.249C>A	p.Asn83Lys	missense_variant	3/8	1	NM_024697.3
ZNF385D-AS1	ENST00000412369.1 linkuse as main transcript	n.181-14588G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000495

AC:

AN:

221998

Hom.:

AF XY:

0.0000496

AC XY:

AN XY:

120938

show subpopulations

Gnomad AFR exome

AF:

0.0000715

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000774

Gnomad OTH exome

AF:

0.000390

GnomAD4 exome

AF:

0.000102

AC:

144

AN:

1405302

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

698980

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000387

Gnomad4 NFE exome

AF:

0.000128

Gnomad4 OTH exome

AF:

0.0000521

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151748

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000255

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.249C>A (p.N83K) alteration is located in exon 3 (coding exon 3) of the ZNF385D gene. This alteration results from a C to A substitution at nucleotide position 249, causing the asparagine (N) at amino acid position 83 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.40

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.93

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.8

D;.

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0050

D;.

Polyphen

1.0

D;.

Vest4

0.83

MutPred

0.68

Gain of methylation at N83 (P = 0.0013);.;

MVP

0.26

MPC

0.20

ClinPred

0.26

GERP RS

5.7

Varity_R

0.80

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over