chr20-63975815-G-C

Variant names:

• chr20-63975815-G-C
• NM_080621.5:c.463C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_080621.5(SAMD10):​c.463C>G​(p.Leu155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAMD10 NM_080621.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89
• 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]

ENSG00000302941 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD10	NM_080621.5	c.463C>G	p.Leu155Val	missense_variant	Exon 4 of 5	ENST00000369886.8	NP_542188.1
SAMD10	XM_011528565.3	c.613C>G	p.Leu205Val	missense_variant	Exon 5 of 6		XP_011526867.2
SAMD10	XM_005260199.5	c.580C>G	p.Leu194Val	missense_variant	Exon 5 of 6		XP_005260256.1
SAMD10	XM_006723705.4	c.481C>G	p.Leu161Val	missense_variant	Exon 5 of 6		XP_006723768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD10	ENST00000369886.8	c.463C>G	p.Leu155Val	missense_variant	Exon 4 of 5	1	NM_080621.5	ENSP00000358902.3
SAMD10	ENST00000478694.1	n.620C>G		non_coding_transcript_exon_variant	Exon 5 of 6	2
SAMD10	ENST00000498830.5	n.527C>G		non_coding_transcript_exon_variant	Exon 4 of 5	2
ENSG00000302941	ENST00000790586.1	n.552-1688G>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.463C>G (p.L155V) alteration is located in exon 4 (coding exon 4) of the SAMD10 gene. This alteration results from a C to G substitution at nucleotide position 463, causing the leucine (L) at amino acid position 155 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.67		Gain of methylation at K159 (P = 0.0711);
MVP		0.62
MPC		1.4
ClinPred		0.96	D
GERP RS		2.0
Varity_R		0.26
gMVP		0.54
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

hg19: chr20-62607168;