1-12847949-C-A

Variant names:

• chr1-12847949-C-A
• NM_001013631.3:c.341G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013631.3(HNRNPCL1):​c.341G>T​(p.Gly114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: HNRNPCL1 NM_001013631.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09109214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPCL1	NM_001013631.3	c.341G>T	p.Gly114Val	missense_variant	Exon 2 of 2	ENST00000317869.7	NP_001013653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPCL1	ENST00000317869.7	c.341G>T	p.Gly114Val	missense_variant	Exon 2 of 2	1	NM_001013631.3	ENSP00000365370.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341G>T (p.G114V) 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 341, causing the glycine (G) at amino acid position 114 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.4
DANN	Benign	0.57
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.055
Sift	Benign	0.040	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.45		Gain of helix (P = 0.0325);
MVP		0.16
MPC		0.043
ClinPred		0.37	T
GERP RS		-0.50
Varity_R		0.047
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-12907802;