7-29924024-A-G

Variant names:

• chr7-29924024-A-G
• NM_014766.5:c.1178T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_014766.5(SCRN1):​c.1178T>C​(p.Leu393Pro) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCRN1 NM_014766.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230

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=0.06969762).
• BP6: Variant 7-29924024-A-G is Benign according to our data. Variant chr7-29924024-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3438473.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRN1	NM_014766.5	c.1178T>C	p.Leu393Pro	missense_variant	Exon 8 of 8	ENST00000242059.10	NP_055581.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCRN1	ENST00000242059.10	c.1178T>C	p.Leu393Pro	missense_variant	Exon 8 of 8	1	NM_014766.5	ENSP00000242059.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 02, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.4
DANN	Benign	0.10
DEOGEN2	Benign	0.0084	T;T;.;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.56	.;T;T;.;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.070	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.79	N;N;.;N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.051
Sift	Benign	0.46	T;T;T;T;T
Sift4G	Benign	0.35	T;T;T;T;T
Polyphen		0.0	B;B;.;B;.
Vest4		0.086
MutPred		0.35		Gain of glycosylation at L393 (P = 0.0116);Gain of glycosylation at L393 (P = 0.0116);.;Gain of glycosylation at L393 (P = 0.0116);.;
MVP		0.099
MPC		0.35
ClinPred		0.11	T
GERP RS		-0.94
Varity_R		0.067
gMVP		0.78

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: chr7-29963640;