Variant 7-29940780-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014766.5(SCRN1):c.641G>C(p.Trp214Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SCRN1
NM_014766.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Variant links:

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]

SCRN1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCRN1	NM_014766.5 linkuse as main transcript	c.641G>C	p.Trp214Ser	missense_variant	5/8	ENST00000242059.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRN1	ENST00000242059.10 linkuse as main transcript	c.641G>C	p.Trp214Ser	missense_variant	5/8	1	NM_014766.5	P1	Q12765-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247294

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458380

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725552

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.701G>C (p.W234S) alteration is located in exon 5 (coding exon 5) of the SCRN1 gene. This alteration results from a G to C substitution at nucleotide position 701, causing the tryptophan (W) at amino acid position 234 to be replaced by a serine (S). 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

Pathogenic

0.63

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.088

T;T;.;T;.;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Pathogenic

3.4

M;M;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-12

D;D;D;D;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0010

D;D;D;D;D;D

Sift4G

Benign

0.068

T;T;D;T;T;.

Polyphen

0.97

D;D;.;D;.;.

Vest4

0.88

MutPred

0.81

Gain of disorder (P = 5e-04);Gain of disorder (P = 5e-04);.;Gain of disorder (P = 5e-04);.;Gain of disorder (P = 5e-04);

MVP

0.57

MPC

1.1

ClinPred

1.0

GERP RS

5.8

Varity_R

0.95

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over