7-64706698-T-C

Variant names:

• chr7-64706698-T-C
• rs1790659061
• NM_001282359.2:c.601T>C

Variant summary

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

The NM_001282359.2(ZNF107):​c.601T>C​(p.Tyr201His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 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)
• Consequence: ZNF107 NM_001282359.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.890
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF107	NM_001282359.2	c.601T>C	p.Tyr201His	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.601T>C	p.Tyr201His	missense_variant	Exon 4 of 4	4	NM_001282359.2	ENSP00000483720.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.394T>C (p.Y132H) alteration is located in exon 7 (coding exon 2) of the ZNF107 gene. This alteration results from a T to C substitution at nucleotide position 394, causing the tyrosine (Y) at amino acid position 132 to be replaced by a histidine (H). 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	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T;.;T;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.00065	N
LIST_S2	Benign	0.16	T;T;.;T;.
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;.;L;L;L
PhyloP100		0.89
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.8	.;.;D;D;D
REVEL	Benign	0.083
Sift	Benign	0.038	.;.;D;D;D
Sift4G	Uncertain	0.035	D;D;D;D;D
Polyphen		1.0	.;.;D;D;D
Vest4		0.26
MutPred		0.79		.;.;Gain of disorder (P = 0.0125);Gain of disorder (P = 0.0125);Gain of disorder (P = 0.0125);
MVP		0.055
MPC		0.012
ClinPred		0.70	D
GERP RS		0.92
Varity_R		0.20
gMVP		0.061
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: rs1790659061; hg19: chr7-64167076;