3-21924618-T-C

Position:

• chr3-21924618-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000494118.5(ZNF385D):​c.326-74899A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,218 control chromosomes in the GnomAD database, including 63,992 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 0.92 (63992 hom., cov: 32)
• Consequence: ZNF385D ENST00000494118.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF385D	XM_011534122.3	c.325+244199A>G		intron_variant			XP_011532424.1
ZNF385D	XM_011534123.3	c.325+244199A>G		intron_variant			XP_011532425.1
ZNF385D	XM_011534124.4	c.325+244199A>G		intron_variant			XP_011532426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF385D	ENST00000494118.5	c.326-74899A>G		intron_variant, NMD_transcript_variant		1		ENSP00000493727
ZNF385D	ENST00000494108.3	c.325+244199A>G		intron_variant		5		ENSP00000495609	P2
ZNF385D	ENST00000706131.1	c.325+244199A>G		intron_variant				ENSP00000516216	A2

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139350 AN: 152098 Hom.: 63933 Cov.: 32

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.916 AC: 139468 AN: 152218 Hom.: 63992 Cov.: 32 AF XY: 0.916 AC XY: 68158 AN XY: 74436

Gnomad4 AFR AF: 0.959

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.912

Alfa AF: 0.903 Hom.: 27657

Bravo AF: 0.923

Asia WGS AF: 0.968 AC: 3365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1694037; hg19: chr3-21966110;