rs1568447814

Variant names:

• chr19-19711491-C-A
• rs1568447814
• NM_021030.3:c.1790G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-19711491-C-A
• chr19-19711491-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021030.3(ZNF14):​c.1790G>T​(p.Arg597Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R597T) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ZNF14 NM_021030.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.45

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055082828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF14	NM_021030.3	c.1790G>T	p.Arg597Ile	missense_variant	Exon 4 of 4	ENST00000344099.4	NP_066358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF14	ENST00000344099.4	c.1790G>T	p.Arg597Ile	missense_variant	Exon 4 of 4	1	NM_021030.3	ENSP00000340514.2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151716 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151836 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74206

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.0
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00017	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.67	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.033
Sift	Benign	0.24	T
Sift4G	Benign	0.18	T
Polyphen		0.0050	B
Vest4		0.21
MutPred		0.46		Loss of catalytic residue at R597 (P = 0.007);
MVP		0.33
MPC		0.19
ClinPred		0.094	T
GERP RS		-0.54
Varity_R		0.053
gMVP		0.022

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

LitVar

Other links and lift over

dbSNP: rs1568447814; hg19: chr19-19822300;