NM_001282359.2:c.793G>T

Variant names:

• chr7-64706890-G-T
• rs769120990
• NM_001282359.2:c.793G>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.793G>T​(p.Ala265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF107 NM_001282359.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.671
• 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=0.102727145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF107	NM_001282359.2	c.793G>T	p.Ala265Ser	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.793G>T	p.Ala265Ser	missense_variant	Exon 4 of 4	4	NM_001282359.2	ENSP00000483720.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152062 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461012 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726820

African (AFR) AF: 0.0000299 AC: 1 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111704

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152062 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74248

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.586G>T (p.A196S) alteration is located in exon 7 (coding exon 2) of the ZNF107 gene. This alteration results from a G to T substitution at nucleotide position 586, causing the alanine (A) at amino acid position 196 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.9
DANN	Benign	0.92
DEOGEN2	Benign	0.025	T;.;T;T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.00018	N
LIST_S2	Benign	0.071	T;T;.;T;.
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.70	.;.;N;N;N
PhyloP100		-0.67
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.8	.;.;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.26	.;.;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.86	.;.;P;P;P
Vest4		0.059
MutPred		0.38		.;.;Gain of ubiquitination at K198 (P = 0.0507);Gain of ubiquitination at K198 (P = 0.0507);Gain of ubiquitination at K198 (P = 0.0507);
MVP		0.055
MPC		0.011
ClinPred		0.13	T
GERP RS		1.4
Varity_R		0.078
gMVP		0.0092
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: rs769120990; hg19: chr7-64167268;