3-21564619-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_024697.3(ZNF385D):c.231G>A(p.Lys77=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00587 in 1,568,812 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (42 hom.)
• Consequence: ZNF385D NM_024697.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61

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-AS1 (HGNC:41136): (ZNF385D antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 3-21564619-C-T is Benign according to our data. Variant chr3-21564619-C-T is described in ClinVar as [Benign]. Clinvar id is 713567.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385D	NM_024697.3	c.231G>A	p.Lys77=	synonymous_variant	3/8	ENST00000281523.8
ZNF385D-AS1	NR_046731.1	n.208-14570C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385D	ENST00000281523.8	c.231G>A	p.Lys77=	synonymous_variant	3/8	1	NM_024697.3
ZNF385D-AS1	ENST00000412369.1	n.181-14570C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00478 AC: 725 AN: 151626 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00136

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00388

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00271

Gnomad FIN AF: 0.00353

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00732

Gnomad OTH AF: 0.00720

GnomAD3 exomes AF: 0.00500 AC: 1141 AN: 228310 Hom.: 5 AF XY: 0.00498 AC XY: 619 AN XY: 124348

Gnomad AFR exome AF: 0.00119

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00823

Gnomad EAS exome AF: 0.0000632

Gnomad SAS exome AF: 0.00207

Gnomad FIN exome AF: 0.00273

Gnomad NFE exome AF: 0.00784

Gnomad OTH exome AF: 0.00508

GnomAD4 exome AF: 0.00599 AC: 8488 AN: 1417068 Hom.: 42 Cov.: 30 AF XY: 0.00595 AC XY: 4191 AN XY: 704956

Gnomad4 AFR exome AF: 0.000855

Gnomad4 AMR exome AF: 0.00321

Gnomad4 ASJ exome AF: 0.00830

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.00223

Gnomad4 FIN exome AF: 0.00237

Gnomad4 NFE exome AF: 0.00689

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.00478 AC: 725 AN: 151744 Hom.: 3 Cov.: 32 AF XY: 0.00410 AC XY: 304 AN XY: 74134

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00387

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00271

Gnomad4 FIN AF: 0.00353

Gnomad4 NFE AF: 0.00732

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00641 Hom.: 4

Bravo AF: 0.00488

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	12
Dann	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs147921825; hg19: chr3-21606111;