chrX-46500265-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2
The NM_001190417.2(ZNF674):c.1309G>T(p.Glu437Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000628 in 1,209,720 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00034 ( 0 hom., 7 hem., cov: 23)
Exomes 𝑓: 0.000035 ( 0 hom. 7 hem. )
Consequence
ZNF674
NM_001190417.2 stop_gained
NM_001190417.2 stop_gained
Scores
1
2
2
Clinical Significance
Conservation
PhyloP100: -1.40
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM4
?
Stoplost variant in NM_001190417.2 Downstream stopcodon found after 8 codons.
BP6
?
Variant X-46500265-C-A is Benign according to our data. Variant chrX-46500265-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3036471.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Hemizygotes in GnomAd at 7 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF674 | NM_001190417.2 | c.1309G>T | p.Glu437Ter | stop_gained | 6/6 | ENST00000683375.1 | |
ZNF674 | NM_001039891.3 | c.1324G>T | p.Glu442Ter | stop_gained | 6/6 | ||
ZNF674 | NM_001146291.2 | c.1306G>T | p.Glu436Ter | stop_gained | 6/6 | ||
ZNF674 | XM_011543943.4 | c.1321G>T | p.Glu441Ter | stop_gained | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF674 | ENST00000683375.1 | c.1309G>T | p.Glu437Ter | stop_gained | 6/6 | NM_001190417.2 | A1 | ||
ZNF674 | ENST00000523374.5 | c.1324G>T | p.Glu442Ter | stop_gained | 6/6 | 1 | P4 | ||
ZNF674 | ENST00000414387.6 | c.1306G>T | p.Glu436Ter | stop_gained | 5/5 | 3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000340 AC: 38AN: 111825Hom.: 0 Cov.: 23 AF XY: 0.000206 AC XY: 7AN XY: 34023
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GnomAD3 exomes AF: 0.0000826 AC: 15AN: 181584Hom.: 0 AF XY: 0.0000297 AC XY: 2AN XY: 67236
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GnomAD4 exome AF: 0.0000346 AC: 38AN: 1097841Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 7AN XY: 363229
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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 | Feb 21, 2022 | 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
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Name
Calibrated prediction
Score
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BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
FATHMM_MKL
Benign
N
MutationTaster
Benign
D;D
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at