rs3821396

Positions:

• chr3-21664877-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.165+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,202 control chromosomes in the GnomAD database, including 11,660 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 0.097 (973 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10687 hom.)
• Consequence: ZNF385D NM_024697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF385D	NM_024697.3	c.165+9C>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.165+9C>T		intron_variant		1	NM_024697.3	ENSP00000281523

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14771 AN: 152054 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0919

GnomAD3 exomes AF: 0.119 AC: 29902 AN: 250658 Hom.: 2138 AF XY: 0.114 AC XY: 15503 AN XY: 135448

Gnomad AFR exome AF: 0.0247

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.0648

Gnomad EAS exome AF: 0.161

Gnomad SAS exome AF: 0.0576

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.115 AC: 168098 AN: 1461030 Hom.: 10687 Cov.: 31 AF XY: 0.113 AC XY: 82371 AN XY: 726840

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.0605

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.0987

GnomAD4 genome AF: 0.0971 AC: 14773 AN: 152172 Hom.: 973 Cov.: 32 AF XY: 0.102 AC XY: 7569 AN XY: 74378

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0613

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.110 Hom.: 2316

Bravo AF: 0.0904

Asia WGS AF: 0.106 AC: 367 AN: 3478

EpiCase AF: 0.106

EpiControl AF: 0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.58

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: rs3821396; hg19: chr3-21706369; COSMIC: COSV55769933;