1-247039440-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033213.5(ZNF670):ā€‹c.101A>Gā€‹(p.Gln34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,605,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000028 ( 0 hom. )

Consequence

ZNF670
NM_033213.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.465
Variant links:
Genes affected
ZNF670 (HGNC:28167): (zinc finger protein 670) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08018452).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF670NM_033213.5 linkuse as main transcriptc.101A>G p.Gln34Arg missense_variant 2/4 ENST00000366503.3 NP_149990.1
ZNF670-ZNF695NR_037894.2 linkuse as main transcriptn.218+39154A>G intron_variant, non_coding_transcript_variant
ZNF670NM_001204220.2 linkuse as main transcriptc.101A>G p.Gln34Arg missense_variant 2/4 NP_001191149.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF670ENST00000366503.3 linkuse as main transcriptc.101A>G p.Gln34Arg missense_variant 2/41 NM_033213.5 ENSP00000355459 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD3 exomes
AF:
0.0000124
AC:
3
AN:
241176
Hom.:
0
AF XY:
0.0000153
AC XY:
2
AN XY:
130780
show subpopulations
Gnomad AFR exome
AF:
0.0000654
Gnomad AMR exome
AF:
0.0000622
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000275
AC:
4
AN:
1453056
Hom.:
0
Cov.:
30
AF XY:
0.00000277
AC XY:
2
AN XY:
722842
show subpopulations
Gnomad4 AFR exome
AF:
0.0000306
Gnomad4 AMR exome
AF:
0.0000699
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 26, 2022The c.101A>G (p.Q34R) alteration is located in exon 2 (coding exon 2) of the ZNF670 gene. This alteration results from a A to G substitution at nucleotide position 101, causing the glutamine (Q) at amino acid position 34 to be replaced by an arginine (R). 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
0.083
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
3.3
DANN
Benign
0.70
DEOGEN2
Benign
0.048
T
Eigen
Benign
-0.91
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.15
T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.39
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.035
Sift
Benign
0.86
T
Sift4G
Benign
0.88
T
Polyphen
0.085
B
Vest4
0.20
MutPred
0.61
Gain of MoRF binding (P = 0.0141);
MVP
0.20
MPC
0.043
ClinPred
0.036
T
GERP RS
-0.75
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.15
gMVP
0.053

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs543432076; hg19: chr1-247202742; API