chr3-21425607-C-T

Variant summary

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

The NM_024697.3(ZNF385D):​c.737G>A​(p.Arg246Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,606,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ZNF385D
NM_024697.3 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87
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]

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 rank MANE Protein UniProt
ZNF385DNM_024697.3 linkc.737G>A p.Arg246Lys missense_variant Exon 6 of 8 ENST00000281523.8 NP_078973.1 Q9H6B1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF385DENST00000281523.8 linkc.737G>A p.Arg246Lys missense_variant Exon 6 of 8 1 NM_024697.3 ENSP00000281523.2 Q9H6B1

Frequencies

GnomAD3 genomes
AF:
0.0000658
AC:
10
AN:
152054
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000203
AC:
5
AN:
245702
Hom.:
0
AF XY:
0.0000226
AC XY:
3
AN XY:
132914
show subpopulations
Gnomad AFR exome
AF:
0.000189
Gnomad AMR exome
AF:
0.0000307
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:
0.00
Gnomad OTH exome
AF:
0.000170
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1454054
Hom.:
0
Cov.:
31
AF XY:
0.0000111
AC XY:
8
AN XY:
723332
show subpopulations
Gnomad4 AFR exome
AF:
0.000422
Gnomad4 AMR exome
AF:
0.000114
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
AF:
0.0000658
AC:
10
AN:
152054
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.000155
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.737G>A (p.R246K) alteration is located in exon 6 (coding exon 6) of the ZNF385D gene. This alteration results from a G to A substitution at nucleotide position 737, causing the arginine (R) at amino acid position 246 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
0.81
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.0060
T
MetaRNN
Uncertain
0.45
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.19
Sift
Uncertain
0.018
D
Sift4G
Uncertain
0.034
D
Polyphen
0.40
B
Vest4
0.67
MutPred
0.55
Gain of solvent accessibility (P = 0.0059);
MVP
0.18
MPC
0.53
ClinPred
0.82
D
GERP RS
5.5
Varity_R
0.56
gMVP
0.50

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.

Other links and lift over

dbSNP: rs764537413; hg19: chr3-21467099; API