chr3-21677754-C-T

Variant names:

• chr3-21677754-C-T
• rs1490157
• NM_024697.3:c.23-12726G>A

Variant summary

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

The NM_024697.3(ZNF385D):​c.23-12726G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 151,746 control chromosomes in the GnomAD database, including 38,978 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 0.71 (38978 hom., cov: 31)
• Consequence: ZNF385D NM_024697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 11 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF385D	NM_024697.3	MANE Select	c.23-12726G>A		intron	N/A	NP_078973.1	Q9H6B1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF385D	ENST00000281523.8	TSL:1 MANE Select	c.23-12726G>A		intron	N/A	ENSP00000281523.2	Q9H6B1
	ZNF385D	ENST00000494118.5	TSL:1	n.390-113070G>A		intron	N/A	ENSP00000493727.1	A0A2R8Y4E5
	ZNF385D	ENST00000706131.1		c.326-12726G>A		intron	N/A	ENSP00000516216.1	A0A994J5P6

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108226 AN: 151628 Hom.: 38944 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.714 AC: 108316 AN: 151746 Hom.: 38978 Cov.: 31 AF XY: 0.717 AC XY: 53172 AN XY: 74140

African (AFR) AF: 0.622 AC: 25749 AN: 41380

American (AMR) AF: 0.765 AC: 11624 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2609 AN: 3466

East Asian (EAS) AF: 0.640 AC: 3288 AN: 5136

South Asian (SAS) AF: 0.686 AC: 3299 AN: 4810

European-Finnish (FIN) AF: 0.829 AC: 8757 AN: 10564

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.747 AC: 50690 AN: 67884

Other (OTH) AF: 0.723 AC: 1522 AN: 2106

Alfa AF: 0.729 Hom.: 62243

Bravo AF: 0.703

Asia WGS AF: 0.636 AC: 2208 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.070
DANN	Benign	0.46
PhyloP100		-1.7
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: rs1490157; hg19: chr3-21719246; COSMIC: COSV55760465;