3-21978302-A-G

Variant names:

• chr3-21978302-A-G
• rs2291818
• ENST00000494118.5:n.326-128583T>C

Variant summary

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

The ENST00000494118.5(ZNF385D):​n.326-128583T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,142 control chromosomes in the GnomAD database, including 6,148 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 0.28 (6147 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: ZNF385D ENST00000494118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 4 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]

ZNF385D-AS2 (HGNC:42420): (ZNF385D antisense RNA 2)

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 = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF385D-AS2	NR_046876.1	n.223+11A>G		intron_variant	Intron 3 of 3
ZNF385D	XM_017007191.2	c.325+190515T>C		intron_variant	Intron 2 of 9		XP_016862680.1
ZNF385D	XM_017007192.2	c.325+190515T>C		intron_variant	Intron 2 of 8		XP_016862681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF385D	ENST00000494118.5	n.326-128583T>C		intron_variant	Intron 2 of 6	1		ENSP00000493727.1
ZNF385D	ENST00000706131.1	c.325+190515T>C		intron_variant	Intron 2 of 9			ENSP00000516216.1
ZNF385D	ENST00000494108.3	c.325+190515T>C		intron_variant	Intron 3 of 9	5		ENSP00000495609.3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42559 AN: 152020 Hom.: 6144 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.280 AC: 42571 AN: 152140 Hom.: 6147 Cov.: 33 AF XY: 0.279 AC XY: 20776 AN XY: 74376

African (AFR) AF: 0.236 AC: 9816 AN: 41528

American (AMR) AF: 0.230 AC: 3519 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1709 AN: 5174

South Asian (SAS) AF: 0.316 AC: 1524 AN: 4822

European-Finnish (FIN) AF: 0.319 AC: 3377 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20853 AN: 67962

Other (OTH) AF: 0.271 AC: 573 AN: 2114

Alfa AF: 0.295 Hom.: 28800

Bravo AF: 0.269

Asia WGS AF: 0.338 AC: 1175 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	4.7
DANN	Benign	0.71
PhyloP100		0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2291818; hg19: chr3-22019794;