3-21751390-A-G

Position:

• chr3-21751390-A-G

Variant summary

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

The ENST00000494118.5(ZNF385D):​c.389+98266T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 1,010,310 control chromosomes in the GnomAD database, including 246,745 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 0.74 (41729 hom., cov: 28)
  • Exomes 𝑓: 0.69 (205016 hom.)
• Consequence: ZNF385D ENST00000494118.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385D	XM_011534122.3	c.326-86362T>C		intron_variant
ZNF385D	XM_011534123.3	c.326-86362T>C		intron_variant
ZNF385D	XM_011534124.4	c.326-86362T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385D	ENST00000494118.5	c.389+98266T>C		intron_variant, NMD_transcript_variant		1
ZNF385D	ENST00000494108.3	c.326-86362T>C		intron_variant		5		P2
ZNF385D	ENST00000706131.1	c.326-86362T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111559 AN: 151390 Hom.: 41693 Cov.: 28

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.689 AC: 591874 AN: 858802 Hom.: 205016 Cov.: 48 AF XY: 0.689 AC XY: 274278 AN XY: 397864

Gnomad4 AFR exome AF: 0.843

Gnomad4 AMR exome AF: 0.704

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.946

Gnomad4 SAS exome AF: 0.735

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.737 AC: 111653 AN: 151508 Hom.: 41729 Cov.: 28 AF XY: 0.736 AC XY: 54432 AN XY: 73984

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.751

Alfa AF: 0.688 Hom.: 45043

Bravo AF: 0.752

Asia WGS AF: 0.847 AC: 2947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	16
DANN	Benign	0.71

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: rs7634827; hg19: chr3-21792882;