NM_014766.5:c.651G>T

Variant names:

• chr7-29940770-C-A
• rs375023545
• NM_014766.5:c.651G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014766.5(SCRN1):​c.651G>T​(p.Glu217Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCRN1 NM_014766.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048309743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRN1	NM_014766.5	c.651G>T	p.Glu217Asp	missense_variant	Exon 5 of 8	ENST00000242059.10	NP_055581.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCRN1	ENST00000242059.10	c.651G>T	p.Glu217Asp	missense_variant	Exon 5 of 8	1	NM_014766.5	ENSP00000242059.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.29
DANN	Benign	0.91
DEOGEN2	Benign	0.0045	T;T;.;T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.65	.;T;T;.;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.048	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.15	N;N;.;N;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.36	T;T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;T;T;.
Polyphen		0.0010	B;B;.;B;.;.
Vest4		0.17
MutPred		0.28		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);.;Loss of loop (P = 0.1242);.;Loss of loop (P = 0.1242);
MVP		0.072
MPC		0.20
ClinPred		0.14	T
GERP RS		-0.85
Varity_R		0.032
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs375023545; hg19: chr7-29980386; COSMIC: COSV54130212; COSMIC: COSV54130212;