Genetic Variant SAMD10:p.Arg27Gln (chr20-63979388-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080621.5(SAMD10):c.80G>A(p.Arg27Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 1,337,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. R27P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

SAMD10
NM_080621.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Publications

0 publications found

Variant links:

Genes affected

SAMD10 (HGNC:16129): (sterile alpha motif domain containing 10) Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be active in cytoplasmic side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SAMD10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118520916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD10	NM_080621.5 link	c.80G>A	p.Arg27Gln	missense_variant	Exon 1 of 5	ENST00000369886.8	NP_542188.1	Q9BYL1
SAMD10	XM_005260199.5 link	c.80G>A	p.Arg27Gln	missense_variant	Exon 1 of 6		XP_005260256.1
SAMD10	XM_006723705.4 link	c.-3G>A		5_prime_UTR_variant	Exon 1 of 6		XP_006723768.1
SAMD10	XM_011528565.3 link	c.141+466G>A		intron_variant	Intron 1 of 5		XP_011526867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SAMD10	ENST00000369886.8 link	c.80G>A	p.Arg27Gln	missense_variant	Exon 1 of 5	1	NM_080621.5	ENSP00000358902.3	Q9BYL1
SAMD10	ENST00000450107.1 link	c.80G>A	p.Arg27Gln	missense_variant	Exon 1 of 3	3		ENSP00000404839.1	Q5JWV3
SAMD10	ENST00000478694.1 link	n.131+466G>A		intron_variant	Intron 1 of 5	2
SAMD10	ENST00000498830.5 link	n.155+466G>A		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000299

AC:

AN:

1337500

Hom.:

Cov.:

AF XY:

0.00000455

AC XY:

AN XY:

659784

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26978

American (AMR)

AF:

0.00

AC:

AN:

29914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23610

East Asian (EAS)

AF:

0.00

AC:

AN:

29394

South Asian (SAS)

AF:

0.0000401

AC:

AN:

74836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5210

European-Non Finnish (NFE)

AF:

9.45e-7

AC:

AN:

1057934

Other (OTH)

AF:

0.00

AC:

AN:

55676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0074

T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.57

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PhyloP100

1.2

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.084

Sift

Benign

0.11

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.084

B;.

Vest4

0.12

MutPred

0.28

Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);

MVP

0.42

MPC

0.55

ClinPred

0.24

GERP RS

2.0

PromoterAI

0.10

Neutral

(source)

Varity_R

0.046

gMVP

0.29

Mutation Taster

=96/4

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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chr20-63979388-C-T

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