Genetic Variant NM_022136.5:c.235A>G (chr21-14516936-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_022136.5(SAMSN1):c.235A>G(p.Lys79Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,584 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SAMSN1
NM_022136.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

Publications

0 publications found

Variant links:

Genes affected

SAMSN1 (HGNC:10528): (SAM domain, SH3 domain and nuclear localization signals 1) SAMSN1 is a member of a novel gene family of putative adaptors and scaffold proteins containing SH3 and SAM (sterile alpha motif) domains (Claudio et al., 2001 [PubMed 11536050]).[supplied by OMIM, Mar 2008]

SAMSN1 links:

LOC124905053 (HGNC:):

LOC124905053 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40317562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022136.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMSN1	NM_022136.5	MANE Select	c.235A>G	p.Lys79Glu	missense	Exon 3 of 8	NP_071419.3
SAMSN1	NM_001395858.1		c.1219A>G	p.Lys407Glu	missense	Exon 13 of 18	NP_001382787.1
SAMSN1	NM_001395857.1		c.1123A>G	p.Lys375Glu	missense	Exon 11 of 16	NP_001382786.1	A0A2R8Y4K8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMSN1	ENST00000400566.6	TSL:1 MANE Select	c.235A>G	p.Lys79Glu	missense	Exon 3 of 8	ENSP00000383411.2	Q9NSI8-1
SAMSN1	ENST00000285670.7	TSL:1	c.439A>G	p.Lys147Glu	missense	Exon 4 of 9	ENSP00000285670.2	Q9NSI8-3
SAMSN1	ENST00000619120.4	TSL:1	c.28A>G	p.Lys10Glu	missense	Exon 4 of 9	ENSP00000480850.1	S6FRS6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248010

AF XY:

0.00000743

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460584

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

85926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111476

Other (OTH)

AF:

0.00

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.083

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.6

PhyloP100

5.1

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.22

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.011

Polyphen

0.87

Vest4

0.35

MutPred

0.32

Loss of methylation at K79 (P = 0.0037)

MVP

0.76

MPC

0.61

ClinPred

0.93

GERP RS

5.3

Varity_R

0.58

gMVP

0.31

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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