Variant chr21-14582274-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001395858.1(SAMSN1):c.903G>T(p.Lys301Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,550,850 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 8 hom. )

Consequence

SAMSN1
NM_001395858.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0950

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:

SAMSN1-AS1 (HGNC:39599): (SAMSN1 antisense RNA 1)

SAMSN1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002650708).

BP6

Variant 21-14582274-C-A is Benign according to our data. Variant chr21-14582274-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 718365.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
SAMSN1	NM_001395858.1 link	c.903G>T	p.Lys301Asn	missense_variant	Exon 11 of 18	NP_001382787.1
SAMSN1	NM_001395857.1 link	c.807G>T	p.Lys269Asn	missense_variant	Exon 9 of 16	NP_001382786.1
SAMSN1	NM_001256370.2 link	c.123G>T	p.Lys41Asn	missense_variant	Exon 2 of 9	NP_001243299.1	Q9NSI8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
SAMSN1	ENST00000285670.7 link	c.123G>T	p.Lys41Asn	missense_variant	Exon 2 of 9	1	ENSP00000285670.2	Q9NSI8-3
SAMSN1	ENST00000647101.1 link	c.807G>T	p.Lys269Asn	missense_variant	Exon 9 of 16		ENSP00000493867.1	A0A2R8Y4K8
SAMSN1-AS1	ENST00000449214.1 link	n.73C>A		non_coding_transcript_exon_variant	Exon 1 of 5	3
SAMSN1	ENST00000644288.1 link	n.298G>T		non_coding_transcript_exon_variant	Exon 2 of 9

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

302

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00170

AC:

256

AN:

150508

Hom.:

AF XY:

0.00151

AC XY:

122

AN XY:

80768

show subpopulations

Gnomad AFR exome

AF:

0.000286

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.000357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.00205

GnomAD4 exome

AF:

0.00250

AC:

3499

AN:

1398534

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1655

AN XY:

689786

show subpopulations

Gnomad4 AFR exome

AF:

0.000411

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.000834

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00209

Gnomad4 NFE exome

AF:

0.00293

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152316

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00340

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00181

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.00100

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.88

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.59

.;N

REVEL

Benign

0.11

Sift

Uncertain

0.0050

.;D

Sift4G

Uncertain

0.035

.;D

Vest4

0.16

MutPred

0.35

.;Loss of methylation at K41 (P = 9e-04);

MVP

0.38

MPC

0.16

ClinPred

0.035

GERP RS

-1.4

gMVP

0.14

Splicing

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