17-82324605-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003004.3(SECTM1):​c.380G>A​(p.Arg127Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,392,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SECTM1
NM_003004.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -7.74
Variant links:
Genes affected
SECTM1 (HGNC:10707): (secreted and transmembrane 1) This gene encodes a transmembrane and secreted protein with characteristics of a type 1a transmembrane protein. It is found in a perinuclear Golgi-like pattern and thought to be involved in hematopoietic and/or immune system processes. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.036515564).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SECTM1NM_003004.3 linkuse as main transcriptc.380G>A p.Arg127Lys missense_variant 3/5 ENST00000269389.8 NP_002995.1 Q8WVN6
SECTM1XM_005256392.4 linkuse as main transcriptc.380G>A p.Arg127Lys missense_variant 3/5 XP_005256449.1 Q8WVN6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SECTM1ENST00000269389.8 linkuse as main transcriptc.380G>A p.Arg127Lys missense_variant 3/51 NM_003004.3 ENSP00000269389.3 Q8WVN6

Frequencies

GnomAD3 genomes
AF:
0.0000139
AC:
2
AN:
143410
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000302
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249770
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135102
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:
0.0000267
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000184
AC:
23
AN:
1249428
Hom.:
0
Cov.:
36
AF XY:
0.0000210
AC XY:
13
AN XY:
618434
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:
0.0000226
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000139
AC:
2
AN:
143410
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
69370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000302
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsAug 05, 2024The c.380G>A (p.R127K) alteration is located in exon 3 (coding exon 2) of the SECTM1 gene. This alteration results from a G to A substitution at nucleotide position 380, causing the arginine (R) at amino acid position 127 to be replaced by a lysine (K). 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
0.18
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.0010
DANN
Benign
0.76
DEOGEN2
Benign
0.0047
T;T;.;.;.
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.0048
N
LIST_S2
Benign
0.29
T;T;T;T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.037
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.;.;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.030
N;.;.;.;.
REVEL
Benign
0.0070
Sift
Benign
0.67
T;.;.;.;.
Sift4G
Benign
0.57
T;T;.;T;.
Polyphen
0.050
B;.;.;.;.
Vest4
0.085
MVP
0.095
MPC
0.49
ClinPred
0.033
T
GERP RS
-7.0
Varity_R
0.037
gMVP
0.087

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.

Other links and lift over

dbSNP: rs141592647; hg19: chr17-80282481; API