chr6-35869652-C-T

Variant names:

• chr6-35869652-C-T
• rs376417169
• NM_003137.5:c.1241G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003137.5(SRPK1):​c.1241G>A​(p.Cys414Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. C414S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRPK1 NM_003137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

Genes affected

SRPK1 (HGNC:11305): (SRSF protein kinase 1) This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. Alternative splicing of this gene results in multiple transcript variants. Additional alternatively spliced transcript variants have been described for this gene, but their full length nature have not been determined.[provided by RefSeq, Jul 2010]

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=0.08228415).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003137.5. 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
	SRPK1	NM_003137.5	MANE Select	c.1241G>A	p.Cys414Tyr	missense	Exon 11 of 16	NP_003128.3
	SRPK1	NR_034069.2		n.1311G>A		non_coding_transcript_exon	Exon 11 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPK1	ENST00000373825.7	TSL:1 MANE Select	c.1241G>A	p.Cys414Tyr	missense	Exon 11 of 16	ENSP00000362931.2	Q96SB4-2
	SRPK1	ENST00000361690.7	TSL:1	c.1289G>A	p.Cys430Tyr	missense	Exon 11 of 16	ENSP00000354674.3	H3BLV9
	SRPK1	ENST00000423325.6	TSL:2	c.1193G>A	p.Cys398Tyr	missense	Exon 11 of 16	ENSP00000391069.2	Q96SB4-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N
PhyloP100		1.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.33		Loss of sheet (P = 3e-04)
MVP		0.44
MPC		0.47
ClinPred		0.25	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.58
Mutation Taster		=73/27	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: rs376417169; hg19: chr6-35837429; COSMIC: COSV60411076; COSMIC: COSV60411076;