chr19-48285836-C-T

Variant names:

• chr19-48285836-C-T
• NM_153608.4:c.212C>T

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.212C>T​(p.Ala71Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• Consequence: ZNF114 NM_153608.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.62
• 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=0.035013914).

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.212C>T	p.Ala71Val	missense	Exon 6 of 6	NP_705836.1	Q8NC26-1
	ZNF114	NM_001331098.1		c.350C>T	p.Ala117Val	missense	Exon 6 of 6	NP_001318027.1
	ZNF114	NM_001331097.1		c.212C>T	p.Ala71Val	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.212C>T	p.Ala71Val	missense	Exon 6 of 6	ENSP00000469998.1	Q8NC26-1
	ZNF114	ENST00000315849.5	TSL:2	c.212C>T	p.Ala71Val	missense	Exon 5 of 5	ENSP00000318898.1	Q8NC26-1
	ZNF114	ENST00000600687.5	TSL:5	c.212C>T	p.Ala71Val	missense	Exon 5 of 5	ENSP00000471727.1	Q8NC26-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.26
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.17
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.3	N
PhyloP100		-2.6
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.0050
Sift	Benign	1.0	T
Sift4G	Benign	0.76	T
Polyphen		0.11	B
Vest4		0.041
MutPred		0.22		Loss of disorder (P = 0.1004)
MVP		0.16
MPC		0.45
ClinPred		0.041	T
GERP RS		0.92
Varity_R		0.021
gMVP		0.058
Mutation Taster		=97/3	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

hg19: chr19-48789093;