7-29968937-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014766.5(SCRN1):c.131C>T(p.Ala44Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000923 in 1,614,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
SCRN1
NM_014766.5 missense
NM_014766.5 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 3.83
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]
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ACMG classification
Classification made for transcript
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=0.013690442).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCRN1 | NM_014766.5 | c.131C>T | p.Ala44Val | missense_variant | 2/8 | ENST00000242059.10 | |
SCRN1 | NM_001145514.1 | c.191C>T | p.Ala64Val | missense_variant | 2/8 | ||
SCRN1 | NM_001145513.1 | c.131C>T | p.Ala44Val | missense_variant | 2/8 | ||
SCRN1 | NM_001145515.2 | c.-45-13577C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCRN1 | ENST00000242059.10 | c.131C>T | p.Ala44Val | missense_variant | 2/8 | 1 | NM_014766.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000578 AC: 88AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000139 AC: 35AN: 251450Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135902
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727238
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GnomAD4 genome AF: 0.000578 AC: 88AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000604 AC XY: 45AN XY: 74462
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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 30, 2023 | The c.191C>T (p.A64V) alteration is located in exon 2 (coding exon 2) of the SCRN1 gene. This alteration results from a C to T substitution at nucleotide position 191, causing the alanine (A) at amino acid position 64 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
N;N;N;N;N;N;N;.
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;.
Sift4G
Benign
T;T;T;T;.;.;T;T
Polyphen
B;B;B;.;.;.;.;.
Vest4
MVP
MPC
0.23
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at