rs388647

Positions:

• chr3-21459131-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024697.3(ZNF385D):​c.440-21928C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,026 control chromosomes in the GnomAD database, including 2,440 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2440 hom., cov: 31)
• Consequence: ZNF385D NM_024697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF385D	NM_024697.3	c.440-21928C>T		intron_variant		ENST00000281523.8	NP_078973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF385D	ENST00000281523.8	c.440-21928C>T		intron_variant		1	NM_024697.3	ENSP00000281523

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26320 AN: 151908 Hom.: 2438 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.173 AC: 26335 AN: 152026 Hom.: 2440 Cov.: 31 AF XY: 0.172 AC XY: 12777 AN XY: 74322

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.186

Alfa AF: 0.196 Hom.: 6190

Bravo AF: 0.174

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	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

Other links and lift over

dbSNP: rs388647; hg19: chr3-21500623;