chr19-53140768-C-T

Variant names:

• chr19-53140768-C-T
• rs914573208
• NM_032584.3:c.2060G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032584.3(ZNF347):​c.2060G>A​(p.Gly687Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF347 NM_032584.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.175
• Publications: 0 publications found

Genes affected

ZNF347 (HGNC:16447): (zinc finger protein 347) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12484014).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032584.3. 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
	ZNF347	NM_032584.3	MANE Select	c.2060G>A	p.Gly687Asp	missense	Exon 5 of 5	NP_115973.2	Q96SE7-1
	ZNF347	NM_001172674.2		c.2063G>A	p.Gly688Asp	missense	Exon 5 of 5	NP_001166145.1	Q96SE7-2
	ZNF347	NM_001172675.2		c.2063G>A	p.Gly688Asp	missense	Exon 5 of 5	NP_001166146.1	Q96SE7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF347	ENST00000334197.12	TSL:1 MANE Select	c.2060G>A	p.Gly687Asp	missense	Exon 5 of 5	ENSP00000334146.6	Q96SE7-1
	ZNF347	ENST00000452676.6	TSL:2	c.2063G>A	p.Gly688Asp	missense	Exon 5 of 5	ENSP00000405218.2	Q96SE7-2
	ZNF347	ENST00000601469.2	TSL:2	c.2063G>A	p.Gly688Asp	missense	Exon 5 of 5	ENSP00000471712.2	Q96SE7-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152076 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249442 AF XY: 0.00000742

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460186 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726320

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111052

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Uncertain	0.45
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.79	N
PhyloP100		0.17
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.043
Sift	Benign	0.17	T
Sift4G	Uncertain	0.038	D
Polyphen		0.99	D
Vest4		0.15
MutPred		0.58		Loss of MoRF binding (P = 0.0381)
MVP		0.22
MPC		0.089
ClinPred		0.65	D
GERP RS		1.5
Varity_R		0.24
gMVP		0.021
Mutation Taster		=99/1	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: rs914573208; hg19: chr19-53644021;