chr3-21677349-T-C

Variant names:

• chr3-21677349-T-C
• rs9816269
• NM_024697.3:c.23-12321A>G

Variant summary

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

The NM_024697.3(ZNF385D):​c.23-12321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 152,106 control chromosomes in the GnomAD database, including 318 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 0.057 (318 hom., cov: 32)
• Consequence: ZNF385D NM_024697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF385D	NM_024697.3	c.23-12321A>G		intron_variant	Intron 1 of 7	ENST00000281523.8	NP_078973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF385D	ENST00000281523.8	c.23-12321A>G		intron_variant	Intron 1 of 7	1	NM_024697.3	ENSP00000281523.2

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8660 AN: 151988 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0572 AC: 8697 AN: 152106 Hom.: 318 Cov.: 32 AF XY: 0.0583 AC XY: 4338 AN XY: 74364

African (AFR) AF: 0.0839 AC: 3485 AN: 41518

American (AMR) AF: 0.0860 AC: 1311 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3472

East Asian (EAS) AF: 0.0664 AC: 342 AN: 5154

South Asian (SAS) AF: 0.0904 AC: 436 AN: 4822

European-Finnish (FIN) AF: 0.0376 AC: 399 AN: 10618

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0346 AC: 2350 AN: 67962

Other (OTH) AF: 0.0630 AC: 133 AN: 2110

Alfa AF: 0.0458 Hom.: 296

Bravo AF: 0.0602

Asia WGS AF: 0.0800 AC: 276 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	0.0020
DANN	Benign	0.68
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9816269; hg19: chr3-21718841;