19-44476985-C-T

Variant names:

• chr19-44476985-C-T
• rs1008237974
• NM_001278509.3:c.1415G>A

Variant summary

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

The NM_001278509.3(ZNF180):​c.1415G>A​(p.Gly472Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,860 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. G472A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF180 NM_001278509.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43
• Publications: 0 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.1415G>A	p.Gly472Glu	missense	Exon 5 of 5	NP_001265438.2	Q9UJW8-2
	ZNF180	NM_013256.7		c.1496G>A	p.Gly499Glu	missense	Exon 5 of 5	NP_037388.3	Q9UJW8-1
	ZNF180	NM_001288759.4		c.1493G>A	p.Gly498Glu	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.1415G>A	p.Gly472Glu	missense	Exon 5 of 5	ENSP00000468021.1	Q9UJW8-2
	ZNF180	ENST00000221327.9	TSL:1	c.1496G>A	p.Gly499Glu	missense	Exon 5 of 5	ENSP00000221327.3
	ZNF180	ENST00000590088.5	TSL:1	n.*1303G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000468523.1	K7ES30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Benign	0.00037	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.32
Sift	Benign	0.34	T
Sift4G	Uncertain	0.060	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.59		Gain of disorder (P = 0.0748)
MVP		0.55
MPC		0.36
ClinPred		0.99	D
GERP RS		5.2
gMVP		0.081
Mutation Taster		=86/14	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: rs1008237974; hg19: chr19-44981202;