5-66159317-C-T

Variant names:

• chr5-66159317-C-T
• rs1744538513
• NM_001077199.3:c.394C>T

Variant summary

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

The NM_001077199.3(SREK1):​c.394C>T​(p.Pro132Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SREK1 NM_001077199.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71
• Publications: 0 publications found

Genes affected

SREK1 (HGNC:17882): (splicing regulatory glutamic acid and lysine rich protein 1) This gene encodes a member of a family of serine/arginine-rich (SR) splicing proteins containing RNA recognition motif (RRM) domains. The encoded protein interacts with other SR proteins to modulate splice site selection. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

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=0.10010439).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077199.3. 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
	SREK1	NM_001077199.3	MANE Select	c.394C>T	p.Pro132Ser	missense	Exon 3 of 12	NP_001070667.1	Q8WXA9-2
	SREK1	NM_001323529.2		c.394C>T	p.Pro132Ser	missense	Exon 3 of 12	NP_001310458.1
	SREK1	NM_001323533.2		c.394C>T	p.Pro132Ser	missense	Exon 3 of 11	NP_001310462.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SREK1	ENST00000334121.11	TSL:2 MANE Select	c.394C>T	p.Pro132Ser	missense	Exon 3 of 12	ENSP00000334538.6	Q8WXA9-2
	SREK1	ENST00000380918.7	TSL:1	c.46C>T	p.Pro16Ser	missense	Exon 4 of 13	ENSP00000370305.3	Q8WXA9-1
	SREK1	ENST00000284041.7	TSL:1	n.327C>T		non_coding_transcript_exon	Exon 3 of 12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.095
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.091
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.030
Sift	Benign	0.97	T
Sift4G	Benign	0.30	T
Polyphen		0.0040	B
Vest4		0.23
MutPred		0.27		Loss of sheet (P = 0.0228)
MVP		0.15
MPC		1.2
ClinPred		0.79	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.76
Mutation Taster		=75/25	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: rs1744538513; hg19: chr5-65455145;