19-8512693-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001146175.2(ZNF414):c.335C>G(p.Ser112Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF414 NM_001146175.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.34

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF414	NM_001146175.2	c.335C>G	p.Ser112Cys	missense_variant	3/8	ENST00000393927.9
ZNF414	NM_032370.3	c.335C>G	p.Ser112Cys	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF414	ENST00000393927.9	c.335C>G	p.Ser112Cys	missense_variant	3/8	1	NM_001146175.2	P1
ZNF414	ENST00000255616.8	c.335C>G	p.Ser112Cys	missense_variant	3/6	1
ZNF414	ENST00000599379.1	c.22C>G	p.Pro8Ala	missense_variant, NMD_transcript_variant	2/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1400462 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 691046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.335C>G (p.S112C) alteration is located in exon 3 (coding exon 3) of the ZNF414 gene. This alteration results from a C to G substitution at nucleotide position 335, causing the serine (S) at amino acid position 112 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Pathogenic	29
Dann	Uncertain	0.99
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		1.0	.;D
Vest4		0.63
MutPred		0.17		Loss of glycosylation at S112 (P = 0.0399);Loss of glycosylation at S112 (P = 0.0399);
MVP		0.52
MPC		0.84
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.34
gMVP		0.30

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-8577577;