19-44477006-G-T

Variant names:

• chr19-44477006-G-T
• rs761815023
• NM_001278509.3:c.1394C>A

Variant summary

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

The NM_001278509.3(ZNF180):​c.1394C>A​(p.Pro465His) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P465L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZNF180 NM_001278509.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278509.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF180	NM_001278509.3	MANE Select	c.1394C>A	p.Pro465His	missense	Exon 5 of 5	NP_001265438.2	Q9UJW8-2
	ZNF180	NM_013256.7		c.1475C>A	p.Pro492His	missense	Exon 5 of 5	NP_037388.3	Q9UJW8-1
	ZNF180	NM_001288759.4		c.1472C>A	p.Pro491His	missense	Exon 5 of 5	NP_001275688.2	Q9UJW8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF180	ENST00000592529.6	TSL:2 MANE Select	c.1394C>A	p.Pro465His	missense	Exon 5 of 5	ENSP00000468021.1	Q9UJW8-2
	ZNF180	ENST00000221327.9	TSL:1	c.1475C>A	p.Pro492His	missense	Exon 5 of 5	ENSP00000221327.3
	ZNF180	ENST00000590088.5	TSL:1	n.*1282C>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000468523.1	K7ES30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251374 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461854 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Benign	0.00018	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.027	T
PhyloP100		4.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-8.9	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.027	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.69		Gain of catalytic residue at E494 (P = 0.1119)
MVP		0.78
MPC		0.35
ClinPred		0.98	D
GERP RS		4.1
gMVP		0.12
Mutation Taster		=89/11	polymorphism

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: rs761815023; hg19: chr19-44981223;