chr2-179483518-T-C

Variant names:

• chr2-179483518-T-C
• rs2271759
• NM_152520.6:c.553-84A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152520.6(ZNF385B):​c.553-84A>G variant causes a intron change. The variant allele was found at a frequency of 0.000000711 in 1,406,440 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF385B NM_152520.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70
• Publications: 0 publications found

Genes affected

ZNF385B (HGNC:26332): (zinc finger protein 385B) Enables p53 binding activity. Involved in intrinsic apoptotic signaling pathway by p53 class mediator. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152520.6. 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
	ZNF385B	NM_152520.6	MANE Select	c.553-84A>G		intron	N/A	NP_689733.4
	ZNF385B	NM_001352809.2		c.691-84A>G		intron	N/A	NP_001339738.1
	ZNF385B	NM_001352810.2		c.553-84A>G		intron	N/A	NP_001339739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF385B	ENST00000410066.7	TSL:1 MANE Select	c.553-84A>G		intron	N/A	ENSP00000386845.2
	ZNF385B	ENST00000466398.5	TSL:1	n.782-84A>G		intron	N/A
	ZNF385B	ENST00000409343.5	TSL:2	c.280-84A>G		intron	N/A	ENSP00000386379.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406440 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 698720

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32314

American (AMR) AF: 0.00 AC: 0 AN: 42702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24346

East Asian (EAS) AF: 0.00 AC: 0 AN: 39144

South Asian (SAS) AF: 0.00 AC: 0 AN: 81092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4094

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1072790

Other (OTH) AF: 0.00 AC: 0 AN: 58240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		3.7

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: rs2271759; hg19: chr2-180348245;