19-53140813-C-T

Variant names:

• chr19-53140813-C-T
• rs145043419
• NM_032584.3:c.2015G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_032584.3(ZNF347):​c.2015G>A​(p.Arg672Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,613,704 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R672G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: ZNF347 NM_032584.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0500
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008690774).
• BP6: Variant 19-53140813-C-T is Benign according to our data. Variant chr19-53140813-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2355771.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2015G>A	p.Arg672Gln	missense	Exon 5 of 5	NP_115973.2	Q96SE7-1
	ZNF347	NM_001172674.2		c.2018G>A	p.Arg673Gln	missense	Exon 5 of 5	NP_001166145.1	Q96SE7-2
	ZNF347	NM_001172675.2		c.2018G>A	p.Arg673Gln	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.2015G>A	p.Arg672Gln	missense	Exon 5 of 5	ENSP00000334146.6	Q96SE7-1
	ZNF347	ENST00000452676.6	TSL:2	c.2018G>A	p.Arg673Gln	missense	Exon 5 of 5	ENSP00000405218.2	Q96SE7-2
	ZNF347	ENST00000601469.2	TSL:2	c.2018G>A	p.Arg673Gln	missense	Exon 5 of 5	ENSP00000471712.2	Q96SE7-2

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 88 AN: 152034 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000263 AC: 66 AN: 250918 AF XY: 0.000258

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000671 AC: 98 AN: 1461552 Hom.: 0 Cov.: 31 AF XY: 0.0000701 AC XY: 51 AN XY: 727064

African (AFR) AF: 0.000149 AC: 5 AN: 33470

American (AMR) AF: 0.00128 AC: 57 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86224

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111826

Other (OTH) AF: 0.0000828 AC: 5 AN: 60376

GnomAD4 genome AF: 0.000578 AC: 88 AN: 152152 Hom.: 1 Cov.: 33 AF XY: 0.000847 AC XY: 63 AN XY: 74398

African (AFR) AF: 0.000120 AC: 5 AN: 41496

American (AMR) AF: 0.00517 AC: 79 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000631

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.080
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.16
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.095	N
PhyloP100		0.050
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.017
Sift	Benign	0.85	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.028
MVP		0.12
MPC		0.013
ClinPred		0.0011	T
GERP RS		1.9
Varity_R		0.016
gMVP		0.013
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: rs145043419; hg19: chr19-53644066; COSMIC: COSV61967707; COSMIC: COSV61967707;