chr19-44477260-T-G

Position:

• chr19-44477260-T-G

Variant summary

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

The NM_001278509.3(ZNF180):​c.1140A>C​(p.Lys380Asn) 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: ZNF180 NM_001278509.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0250

Genes affected

ZNF180 (HGNC:12970): (zinc finger protein 180) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See MIM 604749 for additional information on zinc finger proteins.[supplied by OMIM, Jul 2002]

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=0.2348359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF180	NM_001278509.3	c.1140A>C	p.Lys380Asn	missense_variant	5/5	ENST00000592529.6	NP_001265438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF180	ENST00000592529.6	c.1140A>C	p.Lys380Asn	missense_variant	5/5	2	NM_001278509.3	ENSP00000468021.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

Nov 07, 2024

The c.1221A>C (p.K407N) alteration is located in exon 5 (coding exon 5) of the ZNF180 gene. This alteration results from a A to C substitution at nucleotide position 1221, causing the lysine (K) at amino acid position 407 to be replaced by an asparagine (N). 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	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;T;.
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.5	D;D;.
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.44
MutPred		0.41		Loss of methylation at K407 (P = 0.0011);.;.;
MVP		0.39
MPC		0.35
ClinPred		0.99	D
GERP RS		3.1
gMVP		0.050

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: rs952279986; hg19: chr19-44981477; COSMIC: COSV55424344; COSMIC: COSV55424344;