19-19712181-C-A

Variant names:

• chr19-19712181-C-A
• rs542057752
• NM_021030.3:c.1100G>T

Variant summary

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

The NM_021030.3(ZNF14):​c.1100G>T​(p.Arg367Leu) 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. 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. R367Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF14 NM_021030.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 0 publications found

Genes affected

ZNF14 (HGNC:12924): (zinc finger protein 14) The protein encoded by this gene contains a zinc finger and a Kruppel-associated box (KRAB) domain. KRAB domain is known to be involved in the transcriptional repression of a number of zinc finger proteins. [provided by RefSeq, Jul 2008]

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=0.04836887).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021030.3. 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
	ZNF14	NM_021030.3	MANE Select	c.1100G>T	p.Arg367Leu	missense	Exon 4 of 4	NP_066358.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF14	ENST00000344099.4	TSL:1 MANE Select	c.1100G>T	p.Arg367Leu	missense	Exon 4 of 4	ENSP00000340514.2	P17017

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.6
DANN	Benign	0.74
DEOGEN2	Benign	0.073	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.00011	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.48	N
PhyloP100		-0.32
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.019
Sift	Benign	0.064	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.43		Loss of MoRF binding (P = 0.0211)
MVP		0.15
MPC		0.11
ClinPred		0.077	T
GERP RS		-3.7
Varity_R		0.051
gMVP		0.029
Mutation Taster		=100/0	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: rs542057752; hg19: chr19-19822990;