chr19-36877128-G-C

Position:

• chr19-36877128-G-C

Variant summary

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

The NM_001242472.2(ZNF345):​c.298G>C​(p.Gly100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF345 NM_001242472.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

Genes affected

ZNF345 (HGNC:16367): (zinc finger protein 345) Enables sequence-specific double-stranded 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=0.052182287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF345	NM_001242472.2	c.298G>C	p.Gly100Arg	missense_variant	3/3	ENST00000420450.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF345	ENST00000420450.6	c.298G>C	p.Gly100Arg	missense_variant	3/3	1	NM_001242472.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.0058	T;T;T;T;.;T;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.077	N
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.052	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.39	N;N;N;N;.;N;.;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.35	T
Sift4G	Benign	0.40	T;T;T;T;T;T;T;.
Polyphen		0.22	B;B;B;B;.;B;.;.
Vest4		0.060
MutPred		0.23		Gain of MoRF binding (P = 0.0127);Gain of MoRF binding (P = 0.0127);Gain of MoRF binding (P = 0.0127);Gain of MoRF binding (P = 0.0127);Gain of MoRF binding (P = 0.0127);Gain of MoRF binding (P = 0.0127);Gain of MoRF binding (P = 0.0127);.;
MVP		0.43
MPC		0.18
ClinPred		0.074	T
GERP RS		2.1
Varity_R		0.061
gMVP		0.019

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-37368030;