chr3-21448956-T-A

Variant names:

• chr3-21448956-T-A
• rs447169
• NM_024697.3:c.440-11753A>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.440-11753A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,892 control chromosomes in the GnomAD database, including 31,924 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 0.65 (31924 hom., cov: 32)
• Consequence: ZNF385D NM_024697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF385D	NM_024697.3	MANE Select	c.440-11753A>T		intron	N/A	NP_078973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF385D	ENST00000281523.8	TSL:1 MANE Select	c.440-11753A>T		intron	N/A	ENSP00000281523.2
	ZNF385D	ENST00000494118.5	TSL:1	n.*367+10376A>T		intron	N/A	ENSP00000493727.1
	ZNF385D	ENST00000706131.1		c.743-7214A>T		intron	N/A	ENSP00000516216.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97925 AN: 151776 Hom.: 31890 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.645 AC: 98018 AN: 151892 Hom.: 31924 Cov.: 32 AF XY: 0.651 AC XY: 48311 AN XY: 74234

African (AFR) AF: 0.716 AC: 29656 AN: 41432

American (AMR) AF: 0.673 AC: 10251 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1545 AN: 3468

East Asian (EAS) AF: 0.569 AC: 2944 AN: 5170

South Asian (SAS) AF: 0.671 AC: 3239 AN: 4824

European-Finnish (FIN) AF: 0.674 AC: 7095 AN: 10526

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41195 AN: 67928

Other (OTH) AF: 0.605 AC: 1277 AN: 2112

Alfa AF: 0.505 Hom.: 1393

Bravo AF: 0.646

Asia WGS AF: 0.657 AC: 2277 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.45
PhyloP100		-0.51
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: rs447169; hg19: chr3-21490448;