3-21424063-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024697.3(ZNF385D):​c.854A>C​(p.His285Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

ZNF385D
NM_024697.3 missense, splice_region

Scores

15
3
1
Splicing: ADA: 0.7507
1
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF385DNM_024697.3 linkuse as main transcriptc.854A>C p.His285Pro missense_variant, splice_region_variant 7/8 ENST00000281523.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF385DENST00000281523.8 linkuse as main transcriptc.854A>C p.His285Pro missense_variant, splice_region_variant 7/81 NM_024697.3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsJun 10, 2022The c.854A>C (p.H285P) alteration is located in exon 7 (coding exon 7) of the ZNF385D gene. This alteration results from a A to C substitution at nucleotide position 854, causing the histidine (H) at amino acid position 285 to be replaced by a proline (P). 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
1.0
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.57
CADD
Pathogenic
33
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.51
D
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Pathogenic
0.40
D
MetaRNN
Pathogenic
0.93
D
MetaSVM
Pathogenic
0.90
D
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-9.7
D
REVEL
Pathogenic
0.92
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.91
MutPred
0.69
Gain of glycosylation at S288 (P = 0.0254);
MVP
0.91
MPC
0.86
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.98
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.75
dbscSNV1_RF
Pathogenic
0.74
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-21465555; API