chr7-29936598-G-T

Position:

• chr7-29936598-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16739637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCRN1	NM_014766.5	c.863C>A	p.Ser288Tyr	missense_variant	6/8	ENST00000242059.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRN1	ENST00000242059.10	c.863C>A	p.Ser288Tyr	missense_variant	6/8	1	NM_014766.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2023

The c.923C>A (p.S308Y) alteration is located in exon 6 (coding exon 6) of the SCRN1 gene. This alteration results from a C to A substitution at nucleotide position 923, causing the serine (S) at amino acid position 308 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.76	.;T;T;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	L;L;.;L;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.87	N;N;N;N;N
REVEL	Benign	0.046
Sift	Benign	0.072	T;T;T;T;T
Sift4G	Uncertain	0.041	D;D;D;D;D
Polyphen		0.044	B;B;.;B;.
Vest4		0.47
MutPred		0.30		Gain of catalytic residue at S288 (P = 0.0029);Gain of catalytic residue at S288 (P = 0.0029);.;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-29976214;