3-21536604-T-C

Position:

• chr3-21536604-T-C

Variant summary

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

The ENST00000281523.8(ZNF385D):​c.277-25581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,192 control chromosomes in the GnomAD database, including 70,764 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 0.96 (70764 hom., cov: 32)
• Consequence: ZNF385D ENST00000281523.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

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 = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF385D	NM_024697.3	c.277-25581A>G		intron_variant		ENST00000281523.8	NP_078973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF385D	ENST00000281523.8	c.277-25581A>G		intron_variant		1	NM_024697.3	ENSP00000281523

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146587 AN: 152074 Hom.: 70700 Cov.: 32

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.961

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

GnomAD4 genome AF: 0.964 AC: 146710 AN: 152192 Hom.: 70764 Cov.: 32 AF XY: 0.964 AC XY: 71744 AN XY: 74386

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.963

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.997

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.962

Alfa AF: 0.950 Hom.: 29760

Bravo AF: 0.965

Asia WGS AF: 0.994 AC: 3454 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.65
DANN	Benign	0.64

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: rs161196; hg19: chr3-21578096;