NM_001077199.3:c.49C>T

Variant names:

• chr5-66144425-C-T
• rs780392285
• NM_001077199.3:c.49C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001077199.3(SREK1):​c.49C>T​(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,551,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SREK1 NM_001077199.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02
• 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]

ENSG00000253744 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029132426).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

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.49C>T	p.Pro17Ser	missense	Exon 1 of 12	NP_001070667.1	Q8WXA9-2
	SREK1	NM_001323529.2		c.49C>T	p.Pro17Ser	missense	Exon 1 of 12	NP_001310458.1
	SREK1	NM_001323533.2		c.49C>T	p.Pro17Ser	missense	Exon 1 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.49C>T	p.Pro17Ser	missense	Exon 1 of 12	ENSP00000334538.6	Q8WXA9-2
	SREK1	ENST00000612404.4	TSL:1	c.49C>T	p.Pro17Ser	missense	Exon 1 of 3	ENSP00000481430.1	A0A087WY03
	SREK1	ENST00000522912.5	TSL:1	n.49C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000427935.1	E5RFV3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152264 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000454 AC: 7 AN: 154220 AF XY: 0.0000612

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000642

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000121 AC: 17 AN: 1399300 Hom.: 0 Cov.: 30 AF XY: 0.0000101 AC XY: 7 AN XY: 690200

African (AFR) AF: 0.00 AC: 0 AN: 31580

American (AMR) AF: 0.00 AC: 0 AN: 35724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.000392 AC: 14 AN: 35712

South Asian (SAS) AF: 0.00 AC: 0 AN: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078948

Other (OTH) AF: 0.0000517 AC: 3 AN: 57996

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152382 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74526

African (AFR) AF: 0.00 AC: 0 AN: 41598

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000544 AC: 5

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	0.092
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Benign	0.96
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.070
Sift	Benign	0.064	T
Sift4G	Benign	0.89	T
Polyphen		0.0060	B
Vest4		0.16
MutPred		0.28		Gain of catalytic residue at P17 (P = 0.0387)
MVP		0.24
MPC		1.4
ClinPred		0.24	T
GERP RS		3.9
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
gMVP		0.65
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780392285; hg19: chr5-65440253;