1-45640350-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_021639.5(GPBP1L1):​c.604T>C​(p.Ser202Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

GPBP1L1
NM_021639.5 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.86
Variant links:
Genes affected
GPBP1L1 (HGNC:28843): (GC-rich promoter binding protein 1 like 1) Predicted to enable DNA binding activity and RNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. 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 4 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity GPBL1_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPBP1L1NM_021639.5 linkc.604T>C p.Ser202Pro missense_variant Exon 8 of 13 ENST00000355105.8 NP_067652.1 Q9HC44

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPBP1L1ENST00000355105.8 linkc.604T>C p.Ser202Pro missense_variant Exon 8 of 13 1 NM_021639.5 ENSP00000347224.3 Q9HC44
GPBP1L1ENST00000290795.7 linkc.604T>C p.Ser202Pro missense_variant Exon 7 of 12 5 ENSP00000290795.3 Q9HC44

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251480
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.000369
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461884
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000337
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.000125
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.604T>C (p.S202P) alteration is located in exon 8 (coding exon 5) of the GPBP1L1 gene. This alteration results from a T to C substitution at nucleotide position 604, causing the serine (S) at amino acid position 202 to be replaced by a proline (P). 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
0.25
BayesDel_addAF
Uncertain
0.012
T
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.27
T;T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
.;D
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.66
D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-2.1
N;N
REVEL
Uncertain
0.43
Sift
Benign
0.034
D;D
Sift4G
Uncertain
0.053
T;T
Polyphen
1.0
D;D
Vest4
0.94
MVP
0.36
MPC
0.58
ClinPred
0.44
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.46
gMVP
0.31

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: rs376805372; hg19: chr1-46106022; COSMIC: COSV99321838; COSMIC: COSV99321838; API