19-53140666-C-A

Variant names:

• chr19-53140666-C-A
• rs150489253
• NM_032584.3:c.2162G>T

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.2162G>T​(p.Arg721Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,602,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R721C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000070 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF347 NM_032584.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.89
• Publications: 5 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=0.09741905).

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.2162G>T	p.Arg721Leu	missense	Exon 5 of 5	NP_115973.2	Q96SE7-1
	ZNF347	NM_001172674.2		c.2165G>T	p.Arg722Leu	missense	Exon 5 of 5	NP_001166145.1	Q96SE7-2
	ZNF347	NM_001172675.2		c.2165G>T	p.Arg722Leu	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.2162G>T	p.Arg721Leu	missense	Exon 5 of 5	ENSP00000334146.6	Q96SE7-1
	ZNF347	ENST00000452676.6	TSL:2	c.2165G>T	p.Arg722Leu	missense	Exon 5 of 5	ENSP00000405218.2	Q96SE7-2
	ZNF347	ENST00000601469.2	TSL:2	c.2165G>T	p.Arg722Leu	missense	Exon 5 of 5	ENSP00000471712.2	Q96SE7-2

Frequencies

GnomAD3 genomes AF: 0.00000700 AC: 1 AN: 142924 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: 0.000210

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459768 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726170

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39470

South Asian (SAS) AF: 0.00 AC: 0 AN: 86002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111020

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome AF: 0.00000700 AC: 1 AN: 142924 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 69422

African (AFR) AF: 0.00 AC: 0 AN: 38188

American (AMR) AF: 0.00 AC: 0 AN: 14288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3358

East Asian (EAS) AF: 0.000210 AC: 1 AN: 4758

South Asian (SAS) AF: 0.00 AC: 0 AN: 4492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65340

Other (OTH) AF: 0.00 AC: 0 AN: 1940

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.0
DANN	Benign	0.85
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.73	N
PhyloP100		-5.9
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.011
Sift	Benign	0.094	T
Sift4G	Benign	0.33	T
Polyphen		0.016	B
Vest4		0.19
MutPred		0.29		Loss of catalytic residue at R721 (P = 0.0099)
MVP		0.099
MPC		0.014
ClinPred		0.27	T
GERP RS		-5.2
Varity_R		0.062
gMVP		0.054
Mutation Taster		=98/2	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: rs150489253; hg19: chr19-53643919; COSMIC: COSV100498380; COSMIC: COSV100498380;