19-48286315-C-A

Variant names:

• chr19-48286315-C-A
• rs770666572
• NM_153608.4:c.691C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153608.4(ZNF114):​c.691C>A​(p.Arg231Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R231H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF114 NM_153608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28
• Publications: 0 publications found

Genes affected

ZNF114 (HGNC:12894): (zinc finger protein 114) Enables identical protein binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ZNF114-AS1 (HGNC:53930): (ZNF114 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044762403).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153608.4. 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
	ZNF114	NM_153608.4	MANE Select	c.691C>A	p.Arg231Ser	missense	Exon 6 of 6	NP_705836.1	Q8NC26-1
	ZNF114	NM_001331098.1		c.829C>A	p.Arg277Ser	missense	Exon 6 of 6	NP_001318027.1
	ZNF114	NM_001331097.1		c.691C>A	p.Arg231Ser	missense	Exon 6 of 6	NP_001318026.1	Q8NC26-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF114	ENST00000595607.6	TSL:1 MANE Select	c.691C>A	p.Arg231Ser	missense	Exon 6 of 6	ENSP00000469998.1	Q8NC26-1
	ZNF114	ENST00000315849.5	TSL:2	c.691C>A	p.Arg231Ser	missense	Exon 5 of 5	ENSP00000318898.1	Q8NC26-1
	ZNF114	ENST00000600687.5	TSL:5	c.691C>A	p.Arg231Ser	missense	Exon 5 of 5	ENSP00000471727.1	Q8NC26-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.018
DANN	Benign	0.28
DEOGEN2	Benign	0.011	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.00036	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-3.3
PrimateAI	Benign	0.19	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.020
Sift	Benign	0.48	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.33		Loss of MoRF binding (P = 0.025)
MVP		0.081
MPC		0.24
ClinPred		0.030	T
GERP RS		-3.6
Varity_R		0.075
gMVP		0.060
Mutation Taster		=96/4	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: rs770666572; hg19: chr19-48789572;