NM_014766.5:c.745A>T

Variant names:

• chr7-29936716-T-A
• rs546394546
• NM_014766.5:c.745A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014766.5(SCRN1):​c.745A>T​(p.Ile249Phe) 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: 1.45

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37492013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRN1	NM_014766.5	c.745A>T	p.Ile249Phe	missense_variant	Exon 6 of 8	ENST00000242059.10	NP_055581.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCRN1	ENST00000242059.10	c.745A>T	p.Ile249Phe	missense_variant	Exon 6 of 8	1	NM_014766.5	ENSP00000242059.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.013	T;T;.;T;.
Eigen	Benign	-0.078
Eigen_PC	Benign	0.035
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	.;T;T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.;L;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.46	N;N;N;N;N
REVEL	Benign	0.095
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T
Polyphen		0.023	B;B;.;B;.
Vest4		0.59
MutPred		0.36		Loss of methylation at K244 (P = 0.0863);Loss of methylation at K244 (P = 0.0863);.;Loss of methylation at K244 (P = 0.0863);.;
MVP		0.19
MPC		0.50
ClinPred		0.21	T
GERP RS		5.6
Varity_R		0.043
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs546394546; hg19: chr7-29976332;