6-28995155-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382360.1(ZNF311):​c.1847G>T​(p.Cys616Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZNF311
NM_001382360.1 missense

Scores

4
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91
Variant links:
Genes affected
ZNF311 (HGNC:13847): (zinc finger protein 311) 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF311NM_001382360.1 linkuse as main transcriptc.1847G>T p.Cys616Phe missense_variant 7/7 ENST00000377179.4 NP_001369289.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF311ENST00000377179.4 linkuse as main transcriptc.1847G>T p.Cys616Phe missense_variant 7/75 NM_001382360.1 ENSP00000366384.3 Q5JNZ3
ZNF311ENST00000483450.1 linkuse as main transcriptn.2657G>T non_coding_transcript_exon_variant 6/62

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249110
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135112
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000891
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461774
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000629
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.000331
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000825
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsDec 13, 2021The c.1847G>T (p.C616F) alteration is located in exon 7 (coding exon 6) of the ZNF311 gene. This alteration results from a G to T substitution at nucleotide position 1847, causing the cysteine (C) at amino acid position 616 to be replaced by a phenylalanine (F). 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
Pathogenic
0.87
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.92
D
M_CAP
Benign
0.050
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Uncertain
0.11
D
MutationAssessor
Pathogenic
4.1
H
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-9.6
D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.96
P
Vest4
0.52
MVP
0.95
MPC
0.93
ClinPred
0.97
D
GERP RS
2.9
Varity_R
0.28
gMVP
0.18

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs140167813; hg19: chr6-28962932; API