chr19-52929321-C-G

Variant names:

• chr19-52929321-C-G
• rs2064889913
• ENST00000391777.3:c.284G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001202473.2(ZNF816-ZNF321P):​c.284G>C​(p.Ser95Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF816-ZNF321P NM_001202473.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.63

Genes affected

ZNF816-ZNF321P (HGNC:38879): (ZNF816-ZNF321P readthrough) This locus represents naturally occurring read-through transcription between the zinc finger protein 816 (ZNF816) gene and the zinc finger protein 321 (ZNF321) pseudogene on chromosome 19. The read-through transcript encodes a KRAB domain-containing protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus encoded by exon structure from the downstream pseudogene. [provided by RefSeq, Jan 2011]

ZNF321P (HGNC:13827): (zinc finger protein 321, pseudogene)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1377058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF816-ZNF321P	NM_001202473.2	c.284G>C	p.Ser95Thr	missense_variant	Exon 4 of 4		NP_001189402.1
ZNF321P	NR_037805.1	n.148G>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF816-ZNF321P	ENST00000391777.3	c.284G>C	p.Ser95Thr	missense_variant	Exon 4 of 4	2		ENSP00000375656.3
ZNF321P	ENST00000313956.4	n.155G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2
ZNF321P	ENST00000550843.1	n.77G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.284G>C (p.S95T) alteration is located in exon 4 (coding exon 3) of the ZNF816-ZNF321P gene. This alteration results from a G to C substitution at nucleotide position 284, causing the serine (S) at amino acid position 95 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.81
DANN	Benign	0.96
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.94	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.026
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.050	T
Vest4		0.12
MVP		0.18
MPC		0.10
ClinPred		0.37	T
GERP RS		0.55
gMVP		0.043

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: rs2064889913; hg19: chr19-53432574;