chr19-53068600-C-A

Position:

• chr19-53068600-C-A

Variant summary

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

The NM_001322131.2(ZNF160):​c.1934G>T​(p.Gly645Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF160 NM_001322131.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.475

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20333108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF160	NM_001322131.2	c.1934G>T	p.Gly645Val	missense_variant	6/6	ENST00000683776.1	NP_001309060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF160	ENST00000683776.1	c.1934G>T	p.Gly645Val	missense_variant	6/6		NM_001322131.2	ENSP00000507845.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Aug 10, 2021

The c.1934G>T (p.G645V) alteration is located in exon 7 (coding exon 4) of the ZNF160 gene. This alteration results from a G to T substitution at nucleotide position 1934, causing the glycine (G) at amino acid position 645 to be replaced by a valine (V). 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	0.93
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.12	.;.;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M;M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-7.9	.;D;D;.
REVEL	Benign	0.11
Sift	Uncertain	0.0010	.;D;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.21
MutPred		0.50		Loss of disorder (P = 0.0525);Loss of disorder (P = 0.0525);Loss of disorder (P = 0.0525);.;
MVP		0.25
MPC		0.92
ClinPred		1.0	D
GERP RS		1.4
Varity_R		0.59
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-53571853;