3-21758217-A-T

Variant names:

• chr3-21758217-A-T
• rs4538394
• ENST00000494118.5:n.389+91439T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000494118.5(ZNF385D):​n.389+91439T>A variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF385D	XM_017007191.2	c.326-93189T>A		intron_variant	Intron 2 of 9		XP_016862680.1
ZNF385D	XM_017007192.2	c.326-93189T>A		intron_variant	Intron 2 of 8		XP_016862681.1
ZNF385D	XM_017007193.2	c.112+91439T>A		intron_variant	Intron 2 of 9		XP_016862682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF385D	ENST00000494118.5	n.389+91439T>A		intron_variant	Intron 3 of 6	1		ENSP00000493727.1
ZNF385D	ENST00000706131.1	c.326-93189T>A		intron_variant	Intron 2 of 9			ENSP00000516216.1
ZNF385D	ENST00000494108.3	c.326-93189T>A		intron_variant	Intron 3 of 9	5		ENSP00000495609.3

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

African (AFR) AF: 0.492 AC: 20422 AN: 41466

American (AMR) AF: 0.745 AC: 11390 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2506 AN: 3468

East Asian (EAS) AF: 0.901 AC: 4648 AN: 5160

South Asian (SAS) AF: 0.662 AC: 3194 AN: 4824

European-Finnish (FIN) AF: 0.803 AC: 8508 AN: 10592

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49821 AN: 68008

Other (OTH) AF: 0.682 AC: 1442 AN: 2114

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
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs4538394; hg19: chr3-21799709;