chr7-64706447-G-A

Variant names:

• chr7-64706447-G-A
• rs113699209
• NM_001282359.2:c.350G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001282359.2(ZNF107):​c.350G>A​(p.Cys117Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,728 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ZNF107 NM_001282359.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.840
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021052778).
• BP6: Variant 7-64706447-G-A is Benign according to our data. Variant chr7-64706447-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2390607.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF107	NM_001282359.2	c.350G>A	p.Cys117Tyr	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.350G>A	p.Cys117Tyr	missense_variant	Exon 4 of 4	4	NM_001282359.2	ENSP00000483720.1

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 251184 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461460 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 726968

African (AFR) AF: 0.000807 AC: 27 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86202

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111794

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74442

African (AFR) AF: 0.000986 AC: 41 AN: 41572

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

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: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000419

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 03, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.30
DANN	Benign	0.33
DEOGEN2	Benign	0.059	T;.;T;T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.67	T;T;T;.;T;.
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.021	T;T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.1	.;.;.;M;M;M
PhyloP100		-0.84
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-9.7	.;.;D;D;D;D
REVEL	Benign	0.082
Sift	Benign	0.088	.;.;T;T;T;T
Sift4G	Benign	0.76	T;T;T;T;T;T
Polyphen		0.10	.;.;.;B;B;B
Vest4		0.057
MVP		0.061
MPC		0.0063
ClinPred		0.043	T
GERP RS		-1.7
Varity_R		0.086
gMVP		0.043
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: rs113699209; hg19: chr7-64166825;