NM_001146175.2:c.1145G>T

Variant names:

• chr19-8510719-C-A
• rs2145805646
• NM_001146175.2:c.1145G>T

Variant summary

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

The NM_001146175.2(ZNF414):​c.1145G>T​(p.Gly382Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,397,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: ZNF414 NM_001146175.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.444
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096227586).

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.1145G>T	p.Gly382Val	missense	Exon 8 of 8	NP_001139647.1	Q96IQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF414	ENST00000393927.9	TSL:1 MANE Select	c.1145G>T	p.Gly382Val	missense	Exon 8 of 8	ENSP00000377504.3	Q96IQ9-2
	ZNF414	ENST00000596772.5	TSL:2	c.*79G>T		3_prime_UTR	Exon 3 of 3	ENSP00000471378.1	M0R0Q5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1397356 Hom.: 0 Cov.: 33 AF XY: 0.00000580 AC XY: 4 AN XY: 689230

African (AFR) AF: 0.00 AC: 0 AN: 31528

American (AMR) AF: 0.00 AC: 0 AN: 35542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25120

East Asian (EAS) AF: 0.00 AC: 0 AN: 35598

South Asian (SAS) AF: 0.00 AC: 0 AN: 79000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000464 AC: 5 AN: 1077868

Other (OTH) AF: 0.00 AC: 0 AN: 57902

GnomAD4 genome Cov.: 32

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	Benign	0.21
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.44
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.099
Sift	Benign	0.044	D
Sift4G	Benign	0.16	T
Vest4		0.40
MutPred		0.081		Loss of catalytic residue at G382 (P = 0.3559)
MVP		0.16
MPC		0.96
ClinPred		0.83	D
GERP RS		0.86
gMVP		0.29
Mutation Taster		=94/6	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: rs2145805646; hg19: chr19-8575603;