NM_001384647.1:c.140G>C

Variant names:

• chr19-45688429-C-G
• rs1159084657
• NM_001384647.1:c.140G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001384647.1(SNRPD2):​c.140G>C​(p.Arg47Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 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. R47H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SNRPD2 NM_001384647.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.15
• Publications: 0 publications found

Genes affected

SNRPD2 (HGNC:11159): (small nuclear ribonucleoprotein D2 polypeptide) The protein encoded by this gene belongs to the small nuclear ribonucleoprotein core protein family. It is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384647.1. 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
	SNRPD2	NM_001384647.1	MANE Select	c.140G>C	p.Arg47Pro	missense	Exon 2 of 3	NP_001371576.1	P62316-1
	SNRPD2	NM_004597.6		c.140G>C	p.Arg47Pro	missense	Exon 3 of 4	NP_004588.1	P62316-1
	SNRPD2	NM_001369751.1		c.110G>C	p.Arg37Pro	missense	Exon 3 of 4	NP_001356680.1	P62316-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPD2	ENST00000342669.8	TSL:1 MANE Select	c.140G>C	p.Arg47Pro	missense	Exon 2 of 3	ENSP00000342374.2	P62316-1
	SNRPD2	ENST00000588301.5	TSL:3	c.140G>C	p.Arg47Pro	missense	Exon 3 of 4	ENSP00000465216.1	P62316-1
	SNRPD2	ENST00000391932.7	TSL:2	c.110G>C	p.Arg37Pro	missense	Exon 3 of 4	ENSP00000375798.2	P62316-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.93	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		7.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.019	D
Polyphen		0.023	B
Vest4		0.95
MutPred		0.70		Loss of MoRF binding (P = 0.0047)
MVP		0.81
MPC		2.2
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.95
gMVP		0.98
Mutation Taster		=197/103	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: rs1159084657; hg19: chr19-46191687;