chr3-21751390-A-G

Variant names:

• chr3-21751390-A-G
• rs7634827
• ENST00000494118.5:n.389+98266T>C

Variant summary

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

The ENST00000494118.5(ZNF385D):​n.389+98266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 1,010,310 control chromosomes in the GnomAD database, including 246,745 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 0.74 (41729 hom., cov: 28)
  • Exomes 𝑓: 0.69 (205016 hom.)
• Consequence: ZNF385D ENST00000494118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF385D	NM_024697.3	c.-474T>C		upstream_gene_variant		ENST00000281523.8	NP_078973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF385D	ENST00000281523.8	c.-474T>C		upstream_gene_variant		1	NM_024697.3	ENSP00000281523.2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111559 AN: 151390 Hom.: 41693 Cov.: 28

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.689 AC: 591874 AN: 858802 Hom.: 205016 Cov.: 48 AF XY: 0.689 AC XY: 274278 AN XY: 397864

African (AFR) AF: 0.843 AC: 13812 AN: 16384

American (AMR) AF: 0.704 AC: 1655 AN: 2352

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 3761 AN: 5664

East Asian (EAS) AF: 0.946 AC: 4036 AN: 4266

South Asian (SAS) AF: 0.735 AC: 14374 AN: 19554

European-Finnish (FIN) AF: 0.562 AC: 834 AN: 1484

Middle Eastern (MID) AF: 0.716 AC: 1225 AN: 1710

European-Non Finnish (NFE) AF: 0.683 AC: 531822 AN: 778514

Other (OTH) AF: 0.705 AC: 20355 AN: 28874

GnomAD4 genome AF: 0.737 AC: 111653 AN: 151508 Hom.: 41729 Cov.: 28 AF XY: 0.736 AC XY: 54432 AN XY: 73984

African (AFR) AF: 0.841 AC: 34739 AN: 41306

American (AMR) AF: 0.744 AC: 11321 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3468

East Asian (EAS) AF: 0.939 AC: 4756 AN: 5066

South Asian (SAS) AF: 0.771 AC: 3681 AN: 4776

European-Finnish (FIN) AF: 0.598 AC: 6272 AN: 10494

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46287 AN: 67870

Other (OTH) AF: 0.751 AC: 1582 AN: 2106

Alfa AF: 0.695 Hom.: 59319

Bravo AF: 0.752

Asia WGS AF: 0.847 AC: 2947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		1.2
PromoterAI		-0.0080	Neutral
Mutation Taster		=300/0	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: rs7634827; hg19: chr3-21792882;