rs774469575

Variant names:

• chr1-12847904-C-A
• rs774469575
• NM_001013631.3:c.386G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-12847904-C-A
• chr1-12847904-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013631.3(HNRNPCL1):​c.386G>T​(p.Arg129Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: HNRNPCL1 NM_001013631.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20864725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013631.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPCL1	NM_001013631.3	MANE Select	c.386G>T	p.Arg129Leu	missense	Exon 2 of 2	NP_001013653.1	O60812

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPCL1	ENST00000317869.7	TSL:1 MANE Select	c.386G>T	p.Arg129Leu	missense	Exon 2 of 2	ENSP00000365370.4	O60812

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.48	N
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.12
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.64	P
Vest4		0.40
MutPred		0.46		Loss of disorder (P = 0.0383)
MVP		0.41
MPC		0.15
ClinPred		0.96	D
GERP RS		-0.073
Varity_R		0.11
gMVP		0.49
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs774469575; hg19: chr1-12907757;