Genetic Variant SAMD1:p.Thr163Thr (chr19-14089932-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The ENST00000533683.7(SAMD1):c.489C>G(p.Thr163Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000338 in 148,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T163T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SAMD1
ENST00000533683.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD1	NM_138352.3 link	c.489C>G	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>G	p.Thr163Thr	synonymous_variant	Exon 1 of 5	1	ENSP00000431971.2	E9PIW9
SAMD1	ENST00000269724.5 link	c.-264-570C>G		intron_variant	Intron 1 of 4	5	ENSP00000269724.5	F8WDT5
ENSG00000295841	ENST00000732936.1 link	n.401+9126G>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000338

AC:

AN:

148106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

224810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

130918

African (AFR)

AF:

0.00

AC:

AN:

4192

American (AMR)

AF:

0.00

AC:

AN:

8256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7300

East Asian (EAS)

AF:

0.00

AC:

AN:

10776

South Asian (SAS)

AF:

0.00

AC:

AN:

28296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

964

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

135462

Other (OTH)

AF:

0.00

AC:

AN:

11568

GnomAD4 genome

AF:

0.0000338

AC:

AN:

148106

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

72136

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

40970

American (AMR)

AF:

0.00

AC:

AN:

14910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66404

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.60

PhyloP100

-0.35

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over