chr1-90937700-G-T

Variant summary

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

The NM_201269.3(ZNF644):​c.3473C>A​(p.Pro1158Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ZNF644
NM_201269.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30
Variant links:
Genes affected
ZNF644 (HGNC:29222): (zinc finger protein 644) The protein encoded by this gene is a zinc finger transcription factor that may play a role in eye development. Defects in this gene have been associated with high myopia. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

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=0.062399805).
BS2
High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF644NM_201269.3 linkuse as main transcriptc.3473C>A p.Pro1158Gln missense_variant 4/6 ENST00000337393.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF644ENST00000337393.10 linkuse as main transcriptc.3473C>A p.Pro1158Gln missense_variant 4/61 NM_201269.3 P1Q9H582-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152008
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250852
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135554
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461684
Hom.:
0
Cov.:
33
AF XY:
0.0000193
AC XY:
14
AN XY:
727140
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:
0.0000234
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152008
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74256
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMar 16, 2022The c.3473C>A (p.P1158Q) alteration is located in exon 4 (coding exon 3) of the ZNF644 gene. This alteration results from a C to A substitution at nucleotide position 3473, causing the proline (P) at amino acid position 1158 to be replaced by a glutamine (Q). 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
0.093
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.017
T;T
Eigen
Benign
-0.037
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.87
.;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.062
T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
0.34
N;N
MutationTaster
Benign
1.0
D;D;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.53
N;N
REVEL
Benign
0.20
Sift
Uncertain
0.0080
D;D
Sift4G
Benign
0.35
T;T
Polyphen
0.066
B;B
Vest4
0.28
MutPred
0.15
Loss of glycosylation at S1162 (P = 0.1075);Loss of glycosylation at S1162 (P = 0.1075);
MVP
0.13
MPC
0.44
ClinPred
0.33
T
GERP RS
6.1
Varity_R
0.071
gMVP
0.27

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: rs749326712; hg19: chr1-91403257; API