NM_014766.5:c.863C>A

Variant names:

• chr7-29936598-G-T
• rs1457968907
• NM_014766.5:c.863C>A

Variant summary

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

The NM_014766.5(SCRN1):​c.863C>A​(p.Ser288Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCRN1 NM_014766.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

Genes affected

SCRN1 (HGNC:22192): (secernin 1) This gene likely encodes a member of the secernin family of proteins. A similar protein in rat functions in regulation of exocytosis in mast cells. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

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=0.16739637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014766.5. 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
	SCRN1	NM_014766.5	MANE Select	c.863C>A	p.Ser288Tyr	missense	Exon 6 of 8	NP_055581.3
	SCRN1	NM_001145514.1		c.923C>A	p.Ser308Tyr	missense	Exon 6 of 8	NP_001138986.1	Q12765-2
	SCRN1	NM_001145513.1		c.863C>A	p.Ser288Tyr	missense	Exon 6 of 8	NP_001138985.1	Q12765-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRN1	ENST00000242059.10	TSL:1 MANE Select	c.863C>A	p.Ser288Tyr	missense	Exon 6 of 8	ENSP00000242059.5	Q12765-1
	SCRN1	ENST00000434476.6	TSL:2	c.923C>A	p.Ser308Tyr	missense	Exon 6 of 8	ENSP00000388942.1	Q12765-2
	SCRN1	ENST00000409497.5	TSL:2	c.863C>A	p.Ser288Tyr	missense	Exon 5 of 7	ENSP00000386872.1	Q12765-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.087
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.4
DANN	Benign	0.68
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.046
Sift	Benign	0.072	T
Sift4G	Uncertain	0.041	D
Polyphen		0.044	B
Vest4		0.47
MutPred		0.30		Gain of catalytic residue at S288 (P = 0.0029)
MVP		0.10
MPC		0.35
ClinPred		0.042	T
GERP RS		0.11
Varity_R		0.022
gMVP		0.69
Mutation Taster		=84/16	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: rs1457968907; hg19: chr7-29976214;