NM_001013631.3:c.442C>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001013631.3(HNRNPCL1):​c.442C>A​(p.Leu148Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,606,314 control chromosomes in the GnomAD database, including 7 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000028 ( 7 hom. )

Consequence

HNRNPCL1
NM_001013631.3 missense

Scores

1
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.37
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06272656).
BP6
Variant 1-12847848-G-T is Benign according to our data. Variant chr1-12847848-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638265.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNRNPCL1NM_001013631.3 linkc.442C>A p.Leu148Ile 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.442C>A p.Leu148Ile missense_variant Exon 2 of 2 1 NM_001013631.3 ENSP00000365370.4 O60812

Frequencies

GnomAD3 genomes
AF:
0.0000200
AC:
3
AN:
149944
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000289
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000427
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000485
AC:
12
AN:
247368
Hom.:
4
AF XY:
0.0000447
AC XY:
6
AN XY:
134094
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000121
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000198
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000282
AC:
41
AN:
1456268
Hom.:
7
Cov.:
33
AF XY:
0.0000442
AC XY:
32
AN XY:
724398
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000230
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000350
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000902
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000200
AC:
3
AN:
150046
Hom.:
0
Cov.:
30
AF XY:
0.0000410
AC XY:
3
AN XY:
73168
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000427
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00111
Hom.:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

HNRNPCL1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
7.7
DANN
Benign
0.93
DEOGEN2
Benign
0.0015
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.045
N
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
0.76
N
REVEL
Benign
0.049
Sift
Benign
0.046
D
Sift4G
Benign
0.065
T
Polyphen
0.0
B
Vest4
0.19
MVP
0.12
MPC
0.039
ClinPred
0.048
T
GERP RS
-0.013
Varity_R
0.039
gMVP
0.20

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: rs2359484; hg19: chr1-12907701; COSMIC: COSV58610201; API