rs12636438

Positions:

• chr3-22021785-A-G

Variant summary

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

The ENST00000494118.5(ZNF385D):​c.325+147032T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,954 control chromosomes in the GnomAD database, including 3,521 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 0.18 (3521 hom., cov: 32)
• Consequence: ZNF385D ENST00000494118.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385D	XM_011534122.3	c.325+147032T>C		intron_variant
ZNF385D	XM_011534123.3	c.325+147032T>C		intron_variant
ZNF385D	XM_011534124.4	c.325+147032T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385D	ENST00000494118.5	c.325+147032T>C		intron_variant, NMD_transcript_variant		1
ZNF385D	ENST00000494108.3	c.325+147032T>C		intron_variant		5		P2
ZNF385D	ENST00000706131.1	c.325+147032T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27399 AN: 151836 Hom.: 3520 Cov.: 32

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.180 AC: 27395 AN: 151954 Hom.: 3521 Cov.: 32 AF XY: 0.182 AC XY: 13493 AN XY: 74270

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.216

Alfa AF: 0.207 Hom.: 2644

Bravo AF: 0.198

Asia WGS AF: 0.309 AC: 1077 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	4.2
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12636438; hg19: chr3-22063277;