Genetic Variant SAMD1:p.Thr163Thr (chr19-14089932-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000533683.7(SAMD1):c.489C>T(p.Thr163Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 373,014 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 8 hom. )

Consequence

SAMD1
ENST00000533683.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.351

Publications

0 publications found

Variant links:

Genes affected

SAMD1 (HGNC:17958): (sterile alpha motif domain containing 1) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be located in cytoplasm and extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SAMD1 links:

ENSG00000295841 (HGNC:):

ENSG00000295841 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-14089932-G-A is Benign according to our data. Variant chr19-14089932-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2649409.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.351 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD1	NM_138352.3 link	c.489C>T	p.Thr163Thr	synonymous_variant	Exon 1 of 5		NP_612361.1	Q6SPF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
SAMD1	ENST00000533683.7 link	c.489C>T	p.Thr163Thr	synonymous_variant	Exon 1 of 5	1	ENSP00000431971.2	E9PIW9
SAMD1	ENST00000269724.5 link	c.-264-570C>T		intron_variant	Intron 1 of 4	5	ENSP00000269724.5	F8WDT5
ENSG00000295841	ENST00000732936.1 link	n.401+9126G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000392

AC:

AN:

148104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00603

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000392

Gnomad OTH

AF:

0.000490

GnomAD2 exomes

AF:

0.00332

AC:

AN:

25622

AF XY:

0.00437

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000406

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000562

Gnomad NFE exome

AF:

0.000535

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00160

AC:

360

AN:

224806

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

284

AN XY:

130914

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

4192

American (AMR)

AF:

0.000242

AC:

AN:

8256

Ashkenazi Jewish (ASJ)

AF:

0.000411

AC:

AN:

7300

East Asian (EAS)

AF:

0.00

AC:

AN:

10776

South Asian (SAS)

AF:

0.00958

AC:

271

AN:

28294

European-Finnish (FIN)

AF:

0.0000556

AC:

AN:

17996

Middle Eastern (MID)

AF:

0.00519

AC:

AN:

964

European-Non Finnish (NFE)

AF:

0.000458

AC:

AN:

135460

Other (OTH)

AF:

0.00138

AC:

AN:

11568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000398

AC:

AN:

148208

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

72248

show subpopulations

African (AFR)

AF:

0.0000487

AC:

AN:

41084

American (AMR)

AF:

0.00

AC:

AN:

14930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

5094

South Asian (SAS)

AF:

0.00624

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000392

AC:

AN:

66394

Other (OTH)

AF:

0.000484

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.000283

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SAMD1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

(source)

DANN

Benign

0.91

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over