NM_001146175.2:c.560C>A

Variant names:

• chr19-8511931-G-T
• rs931511521
• NM_001146175.2:c.560C>A

Variant summary

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

The NM_001146175.2(ZNF414):​c.560C>A​(p.Thr187Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000773 in 1,423,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ZNF414 NM_001146175.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96
• Publications: 1 publications found

Genes affected

ZNF414 (HGNC:20630): (zinc finger protein 414) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146175.2. 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
	ZNF414	NM_001146175.2	MANE Select	c.560C>A	p.Thr187Lys	missense	Exon 5 of 8	NP_001139647.1	Q96IQ9-2
	ZNF414	NM_032370.3		c.560C>A	p.Thr187Lys	missense	Exon 5 of 6	NP_115746.2	Q96IQ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF414	ENST00000393927.9	TSL:1 MANE Select	c.560C>A	p.Thr187Lys	missense	Exon 5 of 8	ENSP00000377504.3	Q96IQ9-2
	ZNF414	ENST00000255616.8	TSL:1	c.560C>A	p.Thr187Lys	missense	Exon 5 of 6	ENSP00000255616.7	Q96IQ9-1
	ZNF414	ENST00000593661.5	TSL:3	c.98C>A	p.Thr33Lys	missense	Exon 3 of 5	ENSP00000473079.1	M0R398

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152264 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000157 AC: 2 AN: 1271670 Hom.: 0 Cov.: 42 AF XY: 0.00000162 AC XY: 1 AN XY: 618630

African (AFR) AF: 0.00 AC: 0 AN: 26806

American (AMR) AF: 0.000111 AC: 2 AN: 18014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17500

East Asian (EAS) AF: 0.00 AC: 0 AN: 33382

South Asian (SAS) AF: 0.00 AC: 0 AN: 55754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1030042

Other (OTH) AF: 0.00 AC: 0 AN: 52290

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152264 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.000589 AC: 9 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000831

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.62		Gain of disorder (P = 0.0245)
MVP		0.55
MPC		0.94
ClinPred		0.99	D
GERP RS		4.9
PromoterAI		0.028	Neutral
Varity_R		0.58
gMVP		0.61
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs931511521; hg19: chr19-8576815;