1-930164-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001385641.1(SAMD11):​c.619C>T​(p.Arg207Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,556,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R207Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SAMD11
NM_001385641.1 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71
Variant links:
Genes affected
SAMD11 (HGNC:28706): (sterile alpha motif domain containing 11) Predicted to enable several functions, including histone binding activity; protein domain specific binding activity; and protein self-association. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30310416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAMD11NM_001385641.1 linkc.619C>T p.Arg207Trp missense_variant Exon 3 of 14 ENST00000616016.5 NP_001372570.1
SAMD11NM_001385640.1 linkc.619C>T p.Arg207Trp missense_variant Exon 3 of 14 NP_001372569.1
SAMD11NM_152486.4 linkc.82C>T p.Arg28Trp missense_variant Exon 3 of 14 NP_689699.3 Q96NU1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAMD11ENST00000616016.5 linkc.619C>T p.Arg207Trp missense_variant Exon 3 of 14 5 NM_001385641.1 ENSP00000478421.2 A0A087WU74

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
33
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000125
AC:
2
AN:
159672
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
85436
show subpopulations
Gnomad AFR exome
AF:
0.000118
Gnomad AMR exome
AF:
0.0000397
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000114
AC:
16
AN:
1404090
Hom.:
0
Cov.:
31
AF XY:
0.0000115
AC XY:
8
AN XY:
693198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000935
Gnomad4 AMR exome
AF:
0.0000553
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:
0.00000924
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152308
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74476
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jun 15, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with SAMD11-related conditions. This variant is present in population databases (rs144245409, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 28 of the SAMD11 protein (p.Arg28Trp). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.73
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.;T;T;T;.;T;.;T;.;T
Eigen
Benign
-0.084
Eigen_PC
Benign
0.021
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.30
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
.;.;M;.;.;.;.;.;.;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-6.3
.;D;D;.;.;.;.;.;.;.;.
REVEL
Benign
0.12
Sift
Benign
0.041
.;D;D;.;.;.;.;.;.;.;.
Sift4G
Uncertain
0.055
.;T;T;T;T;T;T;T;T;T;T
Polyphen
0.40
.;.;B;.;.;.;.;.;.;.;.
Vest4
0.73, 0.62, 0.78, 0.71, 0.80, 0.83, 0.86, 0.69
MVP
0.46
MPC
0.040
ClinPred
0.91
D
GERP RS
3.6
Varity_R
0.41
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs144245409; hg19: chr1-865544; API