3-21664877-G-A

Variant names:

• chr3-21664877-G-A
• rs3821396
• NM_024697.3:c.165+9C>T

Variant summary

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

The NM_024697.3(ZNF385D):​c.165+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,202 control chromosomes in the GnomAD database, including 11,660 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 0.097 (973 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10687 hom.)
• Consequence: ZNF385D NM_024697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 18 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF385D	NM_024697.3	c.165+9C>T		intron_variant	Intron 2 of 7	ENST00000281523.8	NP_078973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF385D	ENST00000281523.8	c.165+9C>T		intron_variant	Intron 2 of 7	1	NM_024697.3	ENSP00000281523.2

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14771 AN: 152054 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0919

GnomAD2 exomes AF: 0.119 AC: 29902 AN: 250658 AF XY: 0.114

Gnomad AFR exome AF: 0.0247

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.0648

Gnomad EAS exome AF: 0.161

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.115 AC: 168098 AN: 1461030 Hom.: 10687 Cov.: 31 AF XY: 0.113 AC XY: 82371 AN XY: 726840

African (AFR) AF: 0.0225 AC: 752 AN: 33430

American (AMR) AF: 0.161 AC: 7182 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 1705 AN: 26110

East Asian (EAS) AF: 0.189 AC: 7483 AN: 39670

South Asian (SAS) AF: 0.0605 AC: 5218 AN: 86218

European-Finnish (FIN) AF: 0.203 AC: 10810 AN: 53346

Middle Eastern (MID) AF: 0.0575 AC: 331 AN: 5758

European-Non Finnish (NFE) AF: 0.116 AC: 128662 AN: 1111470

Other (OTH) AF: 0.0987 AC: 5955 AN: 60346

GnomAD4 genome AF: 0.0971 AC: 14773 AN: 152172 Hom.: 973 Cov.: 32 AF XY: 0.102 AC XY: 7569 AN XY: 74378

African (AFR) AF: 0.0258 AC: 1073 AN: 41554

American (AMR) AF: 0.127 AC: 1935 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3470

East Asian (EAS) AF: 0.156 AC: 803 AN: 5160

South Asian (SAS) AF: 0.0613 AC: 296 AN: 4828

European-Finnish (FIN) AF: 0.218 AC: 2312 AN: 10586

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7831 AN: 67988

Other (OTH) AF: 0.0956 AC: 202 AN: 2112

Alfa AF: 0.108 Hom.: 3676

Bravo AF: 0.0904

Asia WGS AF: 0.106 AC: 367 AN: 3478

EpiCase AF: 0.106

EpiControl AF: 0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.58
PhyloP100		0.47
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: rs3821396; hg19: chr3-21706369; COSMIC: COSV55769933;