NM_001013631.3:c.829G>T

Variant names:

• chr1-12847461-C-A
• rs375508132
• NM_001013631.3:c.829G>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.829G>T​(p.Ala277Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00004 in 150,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A277T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HNRNPCL1 NM_001013631.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• 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=0.12577593).

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.829G>T	p.Ala277Ser	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.829G>T	p.Ala277Ser	missense	Exon 2 of 2	ENSP00000365370.4	O60812

Frequencies

GnomAD3 genomes AF: 0.0000400 AC: 6 AN: 150076 Hom.: 0 Cov.: 30

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: 0.000570

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251158 AF XY: 0.0000147

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 FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000117 AC: 17 AN: 1456680 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 724636

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 43462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 85800

European-Finnish (FIN) AF: 0.000319 AC: 17 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109128

Other (OTH) AF: 0.00 AC: 0 AN: 60176

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000400 AC: 6 AN: 150076 Hom.: 0 Cov.: 30 AF XY: 0.0000684 AC XY: 5 AN XY: 73152

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40834

American (AMR) AF: 0.00 AC: 0 AN: 14556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4672

European-Finnish (FIN) AF: 0.000570 AC: 6 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67606

Other (OTH) AF: 0.00 AC: 0 AN: 2066

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000563292), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.45
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.058
Sift	Benign	0.083	T
Sift4G	Benign	0.71	T
Polyphen		1.0	D
Vest4		0.094
MutPred		0.17		Gain of phosphorylation at A277 (P = 4e-04)
MVP		0.42
MPC		0.054
ClinPred		0.27	T
GERP RS		0.93
Varity_R		0.045
gMVP		0.027
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs375508132; hg19: chr1-12907314;