3-21758217-A-T

Variant summary

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

The ENST00000494118.5(ZNF385D):c.389+91439T>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,128 control chromosomes in the GnomAD database, including 35,919 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 0.68 (35919 hom., cov: 32)
• Consequence: ZNF385D ENST00000494118.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385D	XM_011534122.3	c.326-93189T>A		intron_variant
ZNF385D	XM_011534123.3	c.326-93189T>A		intron_variant
ZNF385D	XM_011534124.4	c.326-93189T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385D	ENST00000494118.5	c.389+91439T>A		intron_variant, NMD_transcript_variant		1
ZNF385D	ENST00000494108.3	c.326-93189T>A		intron_variant		5		P2
ZNF385D	ENST00000706131.1	c.326-93189T>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102827 AN: 152010 Hom.: 35904 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.676 AC: 102892 AN: 152128 Hom.: 35919 Cov.: 32 AF XY: 0.682 AC XY: 50737 AN XY: 74358

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.682

Alfa AF: 0.710 Hom.: 4876

Bravo AF: 0.665

Asia WGS AF: 0.763 AC: 2652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.33
Dann	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4538394; hg19: chr3-21799709;