NM_001282359.2:c.346G>T

Variant names:

• chr7-64706443-G-T
• rs144739473
• NM_001282359.2:c.346G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282359.2(ZNF107):​c.346G>T​(p.Gly116Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G116S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF107 NM_001282359.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 0 publications found

Genes affected

ZNF107 (HGNC:12887): (zinc finger protein 107) This gene encodes a protein containing multiple C2H2-type zinc finger regions. Proteins containing zinc fingers may act as transcriptional regulators, but may also have other cellular functions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

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=0.13293031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF107	NM_001282359.2	c.346G>T	p.Gly116Cys	missense_variant	Exon 4 of 4	ENST00000620827.6	NP_001269288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF107	ENST00000620827.6	c.346G>T	p.Gly116Cys	missense_variant	Exon 4 of 4	4	NM_001282359.2	ENSP00000483720.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461408 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726942

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111752

Other (OTH) AF: 0.0000166 AC: 1 AN: 60368

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T;.;T;T;T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.000060	N
LIST_S2	Benign	0.28	T;T;T;.;T;.
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	.;.;.;L;L;L
PhyloP100		0.31
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-7.4	.;.;D;D;D;D
REVEL	Benign	0.075
Sift	Benign	0.14	.;.;T;D;D;D
Sift4G	Benign	0.089	T;T;T;D;D;D
Polyphen		0.12	.;.;.;B;B;B
Vest4		0.15
MutPred		0.45		.;.;Gain of methylation at K46 (P = 0.0171);Gain of methylation at K46 (P = 0.0171);Gain of methylation at K46 (P = 0.0171);Gain of methylation at K46 (P = 0.0171);
MVP		0.18
MPC		0.0083
ClinPred		0.62	D
GERP RS		0.42
Varity_R		0.25
gMVP		0.028
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: rs144739473; hg19: chr7-64166821;