chr20-63979388-C-A

Variant names:

• chr20-63979388-C-A
• rs781093787
• NM_080621.5:c.80G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080621.5(SAMD10):​c.80G>T​(p.Arg27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,337,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000060 (0 hom.)
• Consequence: SAMD10 NM_080621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

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]

ACMG classification

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=0.13360566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD10	NM_080621.5	c.80G>T	p.Arg27Leu	missense_variant	Exon 1 of 5	ENST00000369886.8	NP_542188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD10	ENST00000369886.8	c.80G>T	p.Arg27Leu	missense_variant	Exon 1 of 5	1	NM_080621.5	ENSP00000358902.3
SAMD10	ENST00000450107.1	c.80G>T	p.Arg27Leu	missense_variant	Exon 1 of 3	3		ENSP00000404839.1
SAMD10	ENST00000478694.1	n.131+466G>T		intron_variant	Intron 1 of 5	2
SAMD10	ENST00000498830.5	n.155+466G>T		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000598 AC: 8 AN: 1337500 Hom.: 0 Cov.: 31 AF XY: 0.00000606 AC XY: 4 AN XY: 659784

African (AFR) AF: 0.00 AC: 0 AN: 26978

American (AMR) AF: 0.00 AC: 0 AN: 29914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23610

East Asian (EAS) AF: 0.00 AC: 0 AN: 29394

South Asian (SAS) AF: 0.00 AC: 0 AN: 74836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5210

European-Non Finnish (NFE) AF: 0.00000756 AC: 8 AN: 1057934

Other (OTH) AF: 0.00 AC: 0 AN: 55676

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.57	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		1.2
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.75	N;D
REVEL	Benign	0.040
Sift	Benign	0.045	D;T
Sift4G	Benign	0.21	T;D
Polyphen		0.020	B;.
Vest4		0.29
MutPred		0.41		Loss of disorder (P = 0.028);Loss of disorder (P = 0.028);
MVP		0.33
MPC		0.60
ClinPred		0.30	T
GERP RS		2.0
PromoterAI		-0.0014	Neutral
Varity_R		0.067
gMVP		0.38
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs781093787; hg19: chr20-62610741;