1-12847790-C-T

Variant summary

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

The NM_001013631.3(HNRNPCL1):​c.500G>A​(p.Arg167Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,606,328 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R167P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000014 ( 2 hom. )

Consequence

HNRNPCL1
NM_001013631.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88
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=0.0745869).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNRNPCL1NM_001013631.3 linkc.500G>A p.Arg167Gln 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.500G>A p.Arg167Gln missense_variant Exon 2 of 2 1 NM_001013631.3 ENSP00000365370.4 O60812

Frequencies

GnomAD3 genomes
AF:
0.0000667
AC:
10
AN:
149978
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000172
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000138
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248906
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135000
show subpopulations
Gnomad AFR exome
AF:
0.000192
Gnomad AMR exome
AF:
0.0000296
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:
0.0000137
AC:
20
AN:
1456350
Hom.:
2
Cov.:
33
AF XY:
0.0000124
AC XY:
9
AN XY:
724488
show subpopulations
Gnomad4 AFR exome
AF:
0.000301
Gnomad4 AMR exome
AF:
0.0000230
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000721
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000667
AC:
10
AN:
149978
Hom.:
0
Cov.:
30
AF XY:
0.0000821
AC XY:
6
AN XY:
73092
show subpopulations
Gnomad4 AFR
AF:
0.000172
Gnomad4 AMR
AF:
0.000138
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000988
Hom.:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.500G>A (p.R167Q) alteration is located in exon 2 (coding exon 1) of the HNRNPCL1 gene. This alteration results from a G to A substitution at nucleotide position 500, causing the arginine (R) at amino acid position 167 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
0.089
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
7.7
DANN
Benign
0.81
DEOGEN2
Benign
0.0036
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.38
N
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.075
T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.96
N
REVEL
Benign
0.10
Sift
Benign
0.061
T
Sift4G
Benign
0.11
T
Polyphen
0.020
B
Vest4
0.21
MVP
0.085
MPC
0.041
ClinPred
0.017
T
GERP RS
-2.2
Varity_R
0.044
gMVP
0.26

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: rs760188448; hg19: chr1-12907643; COSMIC: COSV58614997; API