chr19-53068246-C-T

Position:

• chr19-53068246-C-T

Variant summary

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

The NM_001322131.2(ZNF160):​c.2288G>A​(p.Cys763Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF160 NM_001322131.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

Genes affected

ZNF160 (HGNC:12948): (zinc finger protein 160) The protein encoded by this gene is a Kruppel-related zinc finger protein which is characterized by the presence of an N-terminal repressor domain, the Kruppel-associated box (KRAB). The KRAB domain is a potent repressor of transcription; thus this protein may function in transcription regulation. Multiple transcript variants have been found for this gene. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF160	NM_001322131.2	c.2288G>A	p.Cys763Tyr	missense_variant	6/6	ENST00000683776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF160	ENST00000683776.1	c.2288G>A	p.Cys763Tyr	missense_variant	6/6		NM_001322131.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461834 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727214

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2024

The c.2288G>A (p.C763Y) alteration is located in exon 7 (coding exon 4) of the ZNF160 gene. This alteration results from a G to A substitution at nucleotide position 2288, causing the cysteine (C) at amino acid position 763 to be replaced by a tyrosine (Y). 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
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.34	T;T;T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.034	.;.;T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Pathogenic	3.6	H;H;H;.
MutationTaster	Benign	0.84	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-8.6	.;D;D;.
REVEL	Uncertain	0.39
Sift	Benign	0.035	.;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.24	B;B;B;.
Vest4		0.29
MutPred		0.78		Gain of MoRF binding (P = 0.0757);Gain of MoRF binding (P = 0.0757);Gain of MoRF binding (P = 0.0757);.;
MVP		0.73
MPC		1.1
ClinPred		0.93	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
gMVP		0.32

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: rs2084028540; hg19: chr19-53571499;