6-34767971-C-T

Variant names:

• chr6-34767971-C-T
• NM_003093.3:c.224C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_003093.3(SNRPC):​c.224C>T​(p.Ala75Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SNRPC NM_003093.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25
• Publications: 0 publications found

Genes affected

SNRPC (HGNC:11157): (small nuclear ribonucleoprotein polypeptide C) This gene encodes one of the specific protein components of the U1 small nuclear ribonucleoprotein (snRNP) particle required for the formation of the spliceosome. The encoded protein participates in the processing of nuclear precursor messenger RNA splicing. snRNP particles are attacked by autoantibodies frequently produced by patients with connective tissue diseases. The genome contains several pseudogenes of this functional gene. Alternative splicing results in a non-coding transcript variant.[provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2867766).
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003093.3. 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
	SNRPC	NM_003093.3	MANE Select	c.224C>T	p.Ala75Val	missense	Exon 4 of 6	NP_003084.1	P09234
	SNRPC	NR_029472.2		n.220C>T		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPC	ENST00000244520.10	TSL:1 MANE Select	c.224C>T	p.Ala75Val	missense	Exon 4 of 6	ENSP00000244520.5	P09234
	SNRPC	ENST00000374017.3	TSL:2	c.287C>T	p.Ala96Val	missense	Exon 3 of 5	ENSP00000363129.3	A0A0A0MRR7
	SNRPC	ENST00000909265.1		c.224C>T	p.Ala75Val	missense	Exon 4 of 7	ENSP00000579324.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460492 Hom.: 0 Cov.: 35 AF XY: 0.00000826 AC XY: 6 AN XY: 726588

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 86028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111442

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0066	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.11
Sift	Benign	0.069	T
Sift4G	Benign	0.60	T
Polyphen		0.82	P
Vest4		0.46
MutPred		0.25		Gain of sheet (P = 0.0221)
MVP		0.20
MPC		1.4
ClinPred		0.88	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.55
Mutation Taster		=68/32	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

hg19: chr6-34735748;