chr19-53140666-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032584.3(ZNF347):​c.2162G>A​(p.Arg721His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 1,602,820 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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 0.00027 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: ZNF347 NM_032584.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027639002).

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>A	p.Arg721His	missense	Exon 5 of 5	NP_115973.2	Q96SE7-1
	ZNF347	NM_001172674.2		c.2165G>A	p.Arg722His	missense	Exon 5 of 5	NP_001166145.1	Q96SE7-2
	ZNF347	NM_001172675.2		c.2165G>A	p.Arg722His	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>A	p.Arg721His	missense	Exon 5 of 5	ENSP00000334146.6	Q96SE7-1
	ZNF347	ENST00000452676.6	TSL:2	c.2165G>A	p.Arg722His	missense	Exon 5 of 5	ENSP00000405218.2	Q96SE7-2
	ZNF347	ENST00000601469.2	TSL:2	c.2165G>A	p.Arg722His	missense	Exon 5 of 5	ENSP00000471712.2	Q96SE7-2

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 32 AN: 142920 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000786

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000631

Gnomad SAS AF: 0.000445

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000352

Gnomad OTH AF: 0.000515

GnomAD2 exomes AF: 0.000217 AC: 54 AN: 248746 AF XY: 0.000223

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.0000588

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000444

Gnomad FIN exome AF: 0.0000927

Gnomad NFE exome AF: 0.000310

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000257 AC: 375 AN: 1459766 Hom.: 0 Cov.: 31 AF XY: 0.000238 AC XY: 173 AN XY: 726170

African (AFR) AF: 0.0000899 AC: 3 AN: 33358

American (AMR) AF: 0.0000675 AC: 3 AN: 44476

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

East Asian (EAS) AF: 0.0000760 AC: 3 AN: 39470

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86002

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53336

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.000305 AC: 339 AN: 1111018

Other (OTH) AF: 0.000282 AC: 17 AN: 60290

GnomAD4 genome AF: 0.000273 AC: 39 AN: 143054 Hom.: 1 Cov.: 33 AF XY: 0.000244 AC XY: 17 AN XY: 69564

African (AFR) AF: 0.000261 AC: 10 AN: 38308

American (AMR) AF: 0.00 AC: 0 AN: 14312

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

East Asian (EAS) AF: 0.000632 AC: 3 AN: 4748

South Asian (SAS) AF: 0.000445 AC: 2 AN: 4494

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.000352 AC: 23 AN: 65332

Other (OTH) AF: 0.000510 AC: 1 AN: 1960

Alfa AF: 0.000194 Hom.: 0

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000247 AC: 30

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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	Benign	0.13
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.5
DANN	Uncertain	0.97
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.087	T
M_CAP	Benign	0.00082	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-5.9
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.024
Sift	Benign	0.073	T
Sift4G	Benign	0.48	T
Polyphen		0.035	B
Vest4		0.043
MVP		0.13
MPC		0.013
ClinPred		0.11	T
GERP RS		-5.2
Varity_R		0.022
gMVP		0.026
Mutation Taster		=97/3	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: COSV100498114; COSMIC: COSV100498114;