chrX-135287619-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007131.5(ZNF75D):​c.1051C>T​(p.Leu351Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,209,404 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Consequence

ZNF75D
NM_007131.5 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.490
Variant links:
Genes affected
ZNF75D (HGNC:13145): (zinc finger protein 75D) This gene encodes a protein that likely functions as a transcription factor. The protein, which belongs to the ZNF75 family, includes an N-terminal SCAN domain, a KRAB box, and five C2H2-type zinc finger motifs. Another functional gene belonging to this family is located on chromosome 16, while pseudogenes have been identified on chromosomes 11 and 12. Alternative splicing results in multiple transcripts variants. [provided by RefSeq, Jun 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.062082082).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF75DNM_007131.5 linkuse as main transcriptc.1051C>T p.Leu351Phe missense_variant 7/7 ENST00000370766.8 NP_009062.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF75DENST00000370766.8 linkuse as main transcriptc.1051C>T p.Leu351Phe missense_variant 7/71 NM_007131.5 ENSP00000359802 P2P51815-1
ZNF75DENST00000469456.1 linkuse as main transcriptn.823C>T non_coding_transcript_exon_variant 2/21
ZNF75DENST00000370764.1 linkuse as main transcriptc.766C>T p.Leu256Phe missense_variant 4/42 ENSP00000359800 A2P51815-2
ZNF75DENST00000494295.1 linkuse as main transcriptn.828-31842C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000355
AC:
4
AN:
112690
Hom.:
0
Cov.:
24
AF XY:
0.0000287
AC XY:
1
AN XY:
34824
show subpopulations
Gnomad AFR
AF:
0.0000645
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000935
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:
0.0000187
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000166
AC:
3
AN:
180436
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
65782
show subpopulations
Gnomad AFR exome
AF:
0.0000789
Gnomad AMR exome
AF:
0.0000371
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000628
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
12
AN:
1096714
Hom.:
0
Cov.:
32
AF XY:
0.00000552
AC XY:
2
AN XY:
362280
show subpopulations
Gnomad4 AFR exome
AF:
0.0000381
Gnomad4 AMR exome
AF:
0.0000286
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.0000107
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000355
AC:
4
AN:
112690
Hom.:
0
Cov.:
24
AF XY:
0.0000287
AC XY:
1
AN XY:
34824
show subpopulations
Gnomad4 AFR
AF:
0.0000645
Gnomad4 AMR
AF:
0.0000935
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000187
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityNov 23, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
14
DANN
Benign
0.12
DEOGEN2
Benign
0.039
T;.
FATHMM_MKL
Benign
0.00062
N
LIST_S2
Benign
0.040
T;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.062
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.4
M;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.86
N;N
REVEL
Benign
0.034
Sift
Benign
0.54
T;T
Sift4G
Benign
0.18
T;T
Polyphen
0.080
B;.
Vest4
0.027
MutPred
0.32
Gain of methylation at K350 (P = 0.0352);.;
MVP
0.54
MPC
0.60
ClinPred
0.025
T
GERP RS
0.68
Varity_R
0.12
gMVP
0.081

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: rs139656149; hg19: chrX-134421551; API