rs925218809

Variant names:

• chr19-45053123-C-G
• NM_007056.3:c.325C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-45053123-C-G
• chr19-45053123-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007056.3(CLASRP):​c.325C>G​(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R109W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLASRP NM_007056.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

Genes affected

CLASRP (HGNC:17731): (CLK4 associating serine/arginine rich protein) Predicted to be involved in RNA splicing and mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLASRP	NM_007056.3	c.325C>G	p.Arg109Gly	missense_variant	Exon 5 of 21	ENST00000221455.8	NP_008987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLASRP	ENST00000221455.8	c.325C>G	p.Arg109Gly	missense_variant	Exon 5 of 21	1	NM_007056.3	ENSP00000221455.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;.;D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.85	T
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Benign	0.28
Sift	Benign	0.062	T;T;T
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.84
MutPred		0.44		Loss of stability (P = 0.0367);.;Loss of stability (P = 0.0367);
MVP		0.44
MPC		2.0
ClinPred		0.99	D
GERP RS		3.6
gMVP		0.78

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-45556381;