16-3408899-C-T

Variant names:

• chr16-3408899-C-T
• rs761098156
• NM_003450.3:c.1204C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_003450.3(ZNF174):​c.1204C>T​(p.Arg402*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,457,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF174 NM_003450.3 stop_gained
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0280

Genes affected

ZNF174 (HGNC:12963): (zinc finger protein 174) This gene encodes a protein with three Cys2-His2-type zinc fingers in the carboxy-terminus, a putative nuclear localization signal, and an amino-terminus SCAN box which forms homodimers. This protein is believed to function as a transcriptional repressor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

ENSG00000285329 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 16-3408899-C-T is Benign according to our data. Variant chr16-3408899-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 207844.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF174	NM_003450.3	c.1204C>T	p.Arg402*	stop_gained	Exon 3 of 3	ENST00000268655.5	NP_003441.1
ZNF174	NM_001347868.2	c.1204C>T	p.Arg402*	stop_gained	Exon 4 of 4		NP_001334797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF174	ENST00000268655.5	c.1204C>T	p.Arg402*	stop_gained	Exon 3 of 3	1	NM_003450.3	ENSP00000268655.4
ENSG00000285329	ENST00000575785.2	n.211+4251C>T		intron_variant	Intron 2 of 4	4		ENSP00000477472.1
ZNF174	ENST00000571936.5	c.1204C>T	p.Arg402*	stop_gained	Exon 4 of 4	5		ENSP00000460397.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 247894 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1457572 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724614

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000451

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000313 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

-

Medical Research Institute, Tokyo Medical and Dental University

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	35
DANN	Benign	0.92
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.00085	N
Vest4		0.17
GERP RS		1.0

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: rs761098156; hg19: chr16-3458899;