1-12847503-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001013631.3(HNRNPCL1):​c.787G>T​(p.Gly263Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000423 in 1,606,518 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000045 ( 5 hom. )

Consequence

HNRNPCL1
NM_001013631.3 missense

Scores

2
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.89
Variant links:
Genes affected
HNRNPCL1 (HGNC:29295): (heterogeneous nuclear ribonucleoprotein C like 1) Enables identical protein binding activity. 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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2522793).
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNRNPCL1NM_001013631.3 linkc.787G>T p.Gly263Trp missense_variant Exon 2 of 2 ENST00000317869.7 NP_001013653.1 O60812

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HNRNPCL1ENST00000317869.7 linkc.787G>T p.Gly263Trp missense_variant Exon 2 of 2 1 NM_001013631.3 ENSP00000365370.4 O60812

Frequencies

GnomAD3 genomes
AF:
0.0000200
AC:
3
AN:
149870
Hom.:
0
Cov.:
30
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:
0.0000444
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251160
Hom.:
1
AF XY:
0.0000147
AC XY:
2
AN XY:
135788
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000446
AC:
65
AN:
1456648
Hom.:
5
Cov.:
32
AF XY:
0.0000511
AC XY:
37
AN XY:
724624
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:
0.0000188
Gnomad4 NFE exome
AF:
0.0000541
Gnomad4 OTH exome
AF:
0.0000665
GnomAD4 genome
AF:
0.0000200
AC:
3
AN:
149870
Hom.:
0
Cov.:
30
AF XY:
0.0000137
AC XY:
1
AN XY:
73006
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:
0.0000444
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 10, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.787G>T (p.G263W) alteration is located in exon 2 (coding exon 1) of the HNRNPCL1 gene. This alteration results from a G to T substitution at nucleotide position 787, causing the glycine (G) at amino acid position 263 to be replaced by a tryptophan (W). 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
0.21
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.047
T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.045
N
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.084
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.21
MutPred
0.28
Loss of sheet (P = 0.0817);
MVP
0.36
MPC
0.25
ClinPred
0.98
D
GERP RS
1.1
Varity_R
0.15
gMVP
0.064

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: rs1236008801; hg19: chr1-12907356; API