NM_001146175.2:c.601C>G

Variant names:

• chr19-8511890-G-C
• rs770535139
• NM_001146175.2:c.601C>G

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.601C>G​(p.His201Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,260,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. H201N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: ZNF414 NM_001146175.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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=0.14344838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF414	NM_001146175.2	c.601C>G	p.His201Asp	missense_variant	Exon 5 of 8	ENST00000393927.9	NP_001139647.1
ZNF414	NM_032370.3	c.601C>G	p.His201Asp	missense_variant	Exon 5 of 6		NP_115746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF414	ENST00000393927.9	c.601C>G	p.His201Asp	missense_variant	Exon 5 of 8	1	NM_001146175.2	ENSP00000377504.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1260528 Hom.: 0 Cov.: 41 AF XY: 0.00000163 AC XY: 1 AN XY: 612636

African (AFR) AF: 0.00 AC: 0 AN: 25702

American (AMR) AF: 0.00 AC: 0 AN: 16954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17208

East Asian (EAS) AF: 0.00 AC: 0 AN: 32324

South Asian (SAS) AF: 0.00 AC: 0 AN: 55374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3866

European-Non Finnish (NFE) AF: 9.77e-7 AC: 1 AN: 1023686

Other (OTH) AF: 0.00 AC: 0 AN: 51798

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	23
DANN	Benign	0.87
DEOGEN2	Benign	0.0066	.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L
PhyloP100		1.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.16
Sift	Benign	0.054	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.98	.;D
Vest4		0.22
MutPred		0.19		Loss of MoRF binding (P = 0.126);Loss of MoRF binding (P = 0.126);
MVP		0.37
MPC		0.92
ClinPred		0.34	T
GERP RS		3.9
PromoterAI		-0.48	Neutral
Varity_R		0.081
gMVP		0.36
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs770535139; hg19: chr19-8576774;