3-21437137-A-G

Position:

• chr3-21437137-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024697.3(ZNF385D):​c.506T>C​(p.Met169Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF385D NM_024697.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06565437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385D	NM_024697.3	c.506T>C	p.Met169Thr	missense_variant	5/8	ENST00000281523.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385D	ENST00000281523.8	c.506T>C	p.Met169Thr	missense_variant	5/8	1	NM_024697.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.506T>C (p.M169T) alteration is located in exon 5 (coding exon 5) of the ZNF385D gene. This alteration results from a T to C substitution at nucleotide position 506, causing the methionine (M) at amino acid position 169 to be replaced by a threonine (T). 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	Benign	0.080
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.019
Sift	Benign	0.68	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.28		Gain of glycosylation at S167 (P = 0.0301);
MVP		0.043
MPC		0.19
ClinPred		0.14	T
GERP RS		3.5
Varity_R		0.051
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-21478629;