19-44476415-T-A

Variant names:

• chr19-44476415-T-A
• rs141416252
• NM_001278509.3:c.1985A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001278509.3(ZNF180):​c.1985A>T​(p.Tyr662Phe) 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. 14/20 in silico tools predict a benign outcome for this variant. 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. Y662C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF180 NM_001278509.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07777244).

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.1985A>T	p.Tyr662Phe	missense	Exon 5 of 5	NP_001265438.2	Q9UJW8-2
	ZNF180	NM_013256.7		c.2066A>T	p.Tyr689Phe	missense	Exon 5 of 5	NP_037388.3	Q9UJW8-1
	ZNF180	NM_001288759.4		c.2063A>T	p.Tyr688Phe	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.1985A>T	p.Tyr662Phe	missense	Exon 5 of 5	ENSP00000468021.1	Q9UJW8-2
	ZNF180	ENST00000221327.9	TSL:1	c.2066A>T	p.Tyr689Phe	missense	Exon 5 of 5	ENSP00000221327.3
	ZNF180	ENST00000590088.5	TSL:1	n.*1873A>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000468523.1	K7ES30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.89	T
PhyloP100		0.60
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.078
Sift	Uncertain	0.022	D
Sift4G	Benign	0.12	T
Polyphen		0.022	B
Vest4		0.34
MutPred		0.36		Loss of ubiquitination at K687 (P = 0.0738)
MVP		0.067
MPC		0.046
ClinPred		0.058	T
GERP RS		2.1
gMVP		0.041
Mutation Taster		=97/3	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: rs141416252; hg19: chr19-44980632;