1-925969-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001385641.1(SAMD11):​c.565C>T​(p.Pro189Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000138 in 1,612,090 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SAMD11
NM_001385641.1 missense

Scores

6
6
7

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.54
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.051590383).
BP6
Variant 1-925969-C-T is Benign according to our data. Variant chr1-925969-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1648427.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAMD11NM_001385641.1 linkc.565C>T p.Pro189Ser missense_variant Exon 2 of 14 ENST00000616016.5 NP_001372570.1
SAMD11NM_001385640.1 linkc.565C>T p.Pro189Ser missense_variant Exon 2 of 14 NP_001372569.1
SAMD11NM_152486.4 linkc.28C>T p.Pro10Ser missense_variant Exon 2 of 14 NP_689699.3 Q96NU1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAMD11ENST00000616016.5 linkc.565C>T p.Pro189Ser missense_variant Exon 2 of 14 5 NM_001385641.1 ENSP00000478421.2 A0A087WU74

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000216
AC:
54
AN:
249696
Hom.:
0
AF XY:
0.000199
AC XY:
27
AN XY:
135468
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00185
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000139
AC:
203
AN:
1459854
Hom.:
0
Cov.:
31
AF XY:
0.000161
AC XY:
117
AN XY:
726246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00233
Gnomad4 NFE exome
AF:
0.0000692
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152236
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000941
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000105
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.000322
AC:
39

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 18, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.10
T;.;T;T;T;.;T;.;T;.;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.052
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.2
.;.;M;.;.;.;.;.;.;.;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-6.7
.;D;D;.;.;.;.;.;.;.;.
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
.;D;D;.;.;.;.;.;.;.;.
Sift4G
Pathogenic
0.0
.;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;.;.;.;.;.;.
Vest4
0.72, 0.71, 0.75, 0.64, 0.69, 0.76, 0.70, 0.57, 0.74
MutPred
0.38
.;Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP
0.65
MPC
0.040
ClinPred
0.39
T
GERP RS
4.5
Varity_R
0.72
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs200686669; hg19: chr1-861349; API