Genetic Variant NM_001385641.1:c.613C>G (chr1-930158-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001385641.1(SAMD11):c.613C>G(p.Arg205Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,184 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R205W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SAMD11
NM_001385641.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Franklin by Genoox

SAMD11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385641.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD11	NM_001385641.1	MANE Select	c.613C>G	p.Arg205Gly	missense	Exon 3 of 14	NP_001372570.1	A0A087WU74
SAMD11	NM_001385640.1		c.613C>G	p.Arg205Gly	missense	Exon 3 of 14	NP_001372569.1	A0A087WX24
SAMD11	NM_152486.4		c.76C>G	p.Arg26Gly	missense	Exon 3 of 14	NP_689699.3	Q96NU1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD11	ENST00000616016.5	TSL:5 MANE Select	c.613C>G	p.Arg205Gly	missense	Exon 3 of 14	ENSP00000478421.2	A0A087WU74
SAMD11	ENST00000968543.1		c.613C>G	p.Arg205Gly	missense	Exon 3 of 14	ENSP00000638602.1
SAMD11	ENST00000618323.5	TSL:5	c.613C>G	p.Arg205Gly	missense	Exon 3 of 14	ENSP00000480678.2	A0A087WX24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1403184

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

692686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32056

American (AMR)

AF:

0.00

AC:

AN:

36116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25200

East Asian (EAS)

AF:

0.00

AC:

AN:

36498

South Asian (SAS)

AF:

0.00

AC:

AN:

79716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

9.25e-7

AC:

AN:

1081450

Other (OTH)

AF:

0.00

AC:

AN:

58170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.7

PhyloP100

2.9

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.40

Sift

Uncertain

0.0040

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.73

MutPred

0.39

Loss of MoRF binding (P = 0.0146)

MVP

0.42

MPC

0.0074

ClinPred

0.94

GERP RS

4.5

PromoterAI

-0.050

Neutral

(source)

Varity_R

0.88

gMVP

0.39

Mutation Taster

=57/43

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over