chr19-53140364-C-T

Variant names:

• chr19-53140364-C-T
• rs368225234
• NM_032584.3:c.2464G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032584.3(ZNF347):​c.2464G>A​(p.Val822Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,596,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: ZNF347 NM_032584.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.402

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0651786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF347	NM_032584.3	c.2464G>A	p.Val822Met	missense_variant	Exon 5 of 5	ENST00000334197.12	NP_115973.2
ZNF347	NM_001172674.2	c.2467G>A	p.Val823Met	missense_variant	Exon 5 of 5		NP_001166145.1
ZNF347	NM_001172675.2	c.2467G>A	p.Val823Met	missense_variant	Exon 5 of 5		NP_001166146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF347	ENST00000334197.12	c.2464G>A	p.Val822Met	missense_variant	Exon 5 of 5	1	NM_032584.3	ENSP00000334146.6
ZNF347	ENST00000452676.6	c.2467G>A	p.Val823Met	missense_variant	Exon 5 of 5	2		ENSP00000405218.2
ZNF347	ENST00000601469.2	c.2467G>A	p.Val823Met	missense_variant	Exon 5 of 5	2		ENSP00000471712.2
ZNF347	ENST00000601804.5	c.97+8317G>A		intron_variant	Intron 3 of 3	4		ENSP00000470590.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000115 AC: 27 AN: 234832 Hom.: 0 AF XY: 0.000103 AC XY: 13 AN XY: 126720

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000369

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 183 AN: 1444604 Hom.: 0 Cov.: 30 AF XY: 0.000107 AC XY: 77 AN XY: 717848

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.0000240

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.0000380

Gnomad4 NFE exome AF: 0.000157

Gnomad4 OTH exome AF: 0.0000671

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2467G>A (p.V823M) alteration is located in exon 5 (coding exon 4) of the ZNF347 gene. This alteration results from a G to A substitution at nucleotide position 2467, causing the valine (V) at amino acid position 823 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.3
DANN	Benign	0.68
DEOGEN2	Benign	0.027	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.055	T;T;.
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.40	N;N;.
REVEL	Benign	0.067
Sift	Uncertain	0.0060	D;D;.
Sift4G	Benign	0.32	T;T;T
Polyphen		0.92	P;.;.
Vest4		0.078
MVP		0.27
MPC		0.022
ClinPred		0.038	T
GERP RS		-5.8
Varity_R		0.034
gMVP		0.0080

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: rs368225234; hg19: chr19-53643617; COSMIC: COSV61968618; COSMIC: COSV61968618;