rs748866700

Variant names:

• chr19-45815685-C-A
• NM_004819.3:c.3700G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-45815685-C-A
• chr19-45815685-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004819.3(SYMPK):​c.3700G>T​(p.Gly1234Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. G1234S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SYMPK NM_004819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

Genes affected

SYMPK (HGNC:22935): (symplekin scaffold protein) This gene encodes a nuclear protein that functions in the regulation of polyadenylation and promotes gene expression. The protein forms a high-molecular weight complex with components of the polyadenylation machinery. It is thought to serve as a scaffold for recruiting regulatory factors to the polyadenylation complex. It also participates in 3'-end maturation of histone mRNAs, which do not undergo polyadenylation. The protein also localizes to the cytoplasmic plaques of tight junctions in some cell types. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08615902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYMPK	NM_004819.3	c.3700G>T	p.Gly1234Cys	missense_variant	Exon 27 of 27	ENST00000245934.12	NP_004810.2
SYMPK	XM_011527354.2	c.3700G>T	p.Gly1234Cys	missense_variant	Exon 28 of 28		XP_011525656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYMPK	ENST00000245934.12	c.3700G>T	p.Gly1234Cys	missense_variant	Exon 27 of 27	1	NM_004819.3	ENSP00000245934.7

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457660 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 725006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.019
Sift	Benign	0.12	T
Sift4G	Benign	0.083	T
Polyphen		0.18	B
Vest4		0.35
MutPred		0.13		Loss of catalytic residue at A1233 (P = 0.141);
MVP		0.043
MPC		0.051
ClinPred		0.12	T
GERP RS		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.098
gMVP		0.10

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-46318943; COSMIC: COSV99680094; COSMIC: COSV99680094;