chrX-46499955-C-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001190417.2(ZNF674):c.1619G>T(p.Arg540Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,200,287 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 61 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., 33 hem., cov: 23)
Exomes 𝑓: 0.00010 ( 0 hom. 28 hem. )
Consequence
ZNF674
NM_001190417.2 missense
NM_001190417.2 missense
Scores
4
1
12
Clinical Significance
Conservation
PhyloP100: 1.09
Genes affected
ZNF674 (HGNC:17625): (zinc finger protein 674) This gene encodes a zinc finger protein with an N-terminal Kruppel-associated box-containing (KRAB) domain and 11 Kruppel-type C2H2 zinc finger domains. Like other zinc finger proteins, this gene may function as a transcription factor. This gene resides on an area of chromosome X that has been implicated in nonsyndromic X-linked cognitive disabilities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013307571).
BP6
?
Variant X-46499955-C-A is Benign according to our data. Variant chrX-46499955-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034837.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Hemizygotes in GnomAd at 33 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF674 | NM_001190417.2 | c.1619G>T | p.Arg540Ile | missense_variant | 6/6 | ENST00000683375.1 | |
ZNF674 | NM_001039891.3 | c.1634G>T | p.Arg545Ile | missense_variant | 6/6 | ||
ZNF674 | NM_001146291.2 | c.1616G>T | p.Arg539Ile | missense_variant | 6/6 | ||
ZNF674 | XM_011543943.4 | c.1631G>T | p.Arg544Ile | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF674 | ENST00000683375.1 | c.1619G>T | p.Arg540Ile | missense_variant | 6/6 | NM_001190417.2 | A1 | ||
ZNF674 | ENST00000523374.5 | c.1634G>T | p.Arg545Ile | missense_variant | 6/6 | 1 | P4 | ||
ZNF674 | ENST00000414387.6 | c.1616G>T | p.Arg539Ile | missense_variant | 5/5 | 3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00110 AC: 123AN: 111872Hom.: 0 Cov.: 23 AF XY: 0.000969 AC XY: 33AN XY: 34042
GnomAD3 genomes
?
AF:
AC:
123
AN:
111872
Hom.:
Cov.:
23
AF XY:
AC XY:
33
AN XY:
34042
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000265 AC: 45AN: 169563Hom.: 0 AF XY: 0.000231 AC XY: 13AN XY: 56187
GnomAD3 exomes
AF:
AC:
45
AN:
169563
Hom.:
AF XY:
AC XY:
13
AN XY:
56187
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000101 AC: 110AN: 1088363Hom.: 0 Cov.: 30 AF XY: 0.0000787 AC XY: 28AN XY: 355607
GnomAD4 exome
AF:
AC:
110
AN:
1088363
Hom.:
Cov.:
30
AF XY:
AC XY:
28
AN XY:
355607
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00110 AC: 123AN: 111924Hom.: 0 Cov.: 23 AF XY: 0.000968 AC XY: 33AN XY: 34104
GnomAD4 genome
?
AF:
AC:
123
AN:
111924
Hom.:
Cov.:
23
AF XY:
AC XY:
33
AN XY:
34104
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
16
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
38
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ZNF674-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 14, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at