1-930158-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385641.1(SAMD11):​c.613C>T​(p.Arg205Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,555,374 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SAMD11
NM_001385641.1 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAMD11NM_001385641.1 linkc.613C>T p.Arg205Trp missense_variant Exon 3 of 14 ENST00000616016.5 NP_001372570.1
SAMD11NM_001385640.1 linkc.613C>T p.Arg205Trp missense_variant Exon 3 of 14 NP_001372569.1
SAMD11NM_152486.4 linkc.76C>T p.Arg26Trp 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.613C>T p.Arg205Trp missense_variant Exon 3 of 14 5 NM_001385641.1 ENSP00000478421.2 A0A087WU74

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000107
AC:
15
AN:
1403184
Hom.:
0
Cov.:
31
AF XY:
0.0000115
AC XY:
8
AN XY:
692686
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:
0.0000502
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000925
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152190
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Oct 25, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 26 of the SAMD11 protein (p.Arg26Trp). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SAMD11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1502618). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.;T;T;T;.;T;.;T;.;T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
0.086
D
MetaRNN
Uncertain
0.71
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Uncertain
2.4
.;.;M;.;.;.;.;.;.;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-6.7
.;D;D;.;.;.;.;.;.;.;.
REVEL
Uncertain
0.46
Sift
Uncertain
0.0010
.;D;D;.;.;.;.;.;.;.;.
Sift4G
Uncertain
0.010
.;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;.;.;.;.;.;.
Vest4
0.73, 0.71, 0.72, 0.74, 0.80, 0.81, 0.80, 0.63, 0.83
MutPred
0.47
.;Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);
MVP
0.56
MPC
0.038
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.78
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs1381099827; hg19: chr1-865538; API