chr20-63979388-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_080621.5(SAMD10):​c.80G>C​(p.Arg27Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000485 in 1,489,232 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00049 (1 hom.)
• Consequence: SAMD10 NM_080621.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.048185647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD10	NM_080621.5	c.80G>C	p.Arg27Pro	missense_variant	Exon 1 of 5	ENST00000369886.8	NP_542188.1
SAMD10	XM_005260199.5	c.80G>C	p.Arg27Pro	missense_variant	Exon 1 of 6		XP_005260256.1
SAMD10	XM_006723705.4	c.-3G>C		5_prime_UTR_variant	Exon 1 of 6		XP_006723768.1
SAMD10	XM_011528565.3	c.141+466G>C		intron_variant	Intron 1 of 5		XP_011526867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD10	ENST00000369886.8	c.80G>C	p.Arg27Pro	missense_variant	Exon 1 of 5	1	NM_080621.5	ENSP00000358902.3
SAMD10	ENST00000450107.1	c.80G>C	p.Arg27Pro	missense_variant	Exon 1 of 3	3		ENSP00000404839.1
SAMD10	ENST00000478694.1	n.131+466G>C		intron_variant	Intron 1 of 5	2
SAMD10	ENST00000498830.5	n.155+466G>C		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.000455 AC: 69 AN: 151732 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000958

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000253 AC: 23 AN: 90734 AF XY: 0.000274

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000180

Gnomad NFE exome AF: 0.000628

Gnomad OTH exome AF: 0.000372

GnomAD4 exome AF: 0.000488 AC: 653 AN: 1337500 Hom.: 1 Cov.: 31 AF XY: 0.000502 AC XY: 331 AN XY: 659784

African (AFR) AF: 0.0000741 AC: 2 AN: 26978

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

Ashkenazi Jewish (ASJ) AF: 0.0000424 AC: 1 AN: 23610

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

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74836

European-Finnish (FIN) AF: 0.000177 AC: 6 AN: 33948

Middle Eastern (MID) AF: 0.000192 AC: 1 AN: 5210

European-Non Finnish (NFE) AF: 0.000589 AC: 623 AN: 1057934

Other (OTH) AF: 0.000341 AC: 19 AN: 55676

GnomAD4 genome AF: 0.000455 AC: 69 AN: 151732 Hom.: 0 Cov.: 31 AF XY: 0.000405 AC XY: 30 AN XY: 74136

African (AFR) AF: 0.0000484 AC: 2 AN: 41346

American (AMR) AF: 0.000131 AC: 2 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000958 AC: 65 AN: 67824

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.000803 Hom.: 0

Bravo AF: 0.000393

ExAC AF: 0.000155 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80G>C (p.R27P) alteration is located in exon 1 (coding exon 1) of the SAMD10 gene. This alteration results from a G to C substitution at nucleotide position 80, causing the arginine (R) at amino acid position 27 to be replaced by a proline (P). 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	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.0072	T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.46	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		1.2
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.031
Sift	Benign	0.23	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0	B;.
Vest4		0.21
MVP		0.39
MPC		0.68
ClinPred		0.061	T
GERP RS		2.0
PromoterAI		0.36	Neutral
Varity_R		0.18
gMVP		0.41
Mutation Taster		=83/17	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; COSMIC: COSV53870492; COSMIC: COSV53870492;