Genetic Variant SAMD11:p.Pro189Ser (chr1-925969-C-T) – ACMG Classification: Likely_benign (-4 pts)

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

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]

SAMD11 links:

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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
SAMD11	NM_001385641.1 link	c.565C>T	p.Pro189Ser	missense_variant	Exon 2 of 14	ENST00000616016.5	NP_001372570.1
SAMD11	NM_001385640.1 link	c.565C>T	p.Pro189Ser	missense_variant	Exon 2 of 14		NP_001372569.1
SAMD11	NM_152486.4 link	c.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
SAMD11	ENST00000616016.5 link	c.565C>T	p.Pro189Ser	missense_variant	Exon 2 of 14	5	NM_001385641.1	ENSP00000478421.2		A0A087WU74

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152236

Hom.:

Cov.:

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:

AN:

249696

Hom.:

AF XY:

0.000199

AC XY:

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.:

Cov.:

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:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

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.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000322

AC:

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

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

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

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.052

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.2

.;.;M;.;.;.;.;.;.;.;.

PrimateAI

Pathogenic

0.82

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over