21-14512509-G-C

Variant names:

• chr21-14512509-G-C
• NM_022136.5:c.344C>G

Variant summary

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

The NM_022136.5(SAMSN1):​c.344C>G​(p.Thr115Arg) 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 benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMSN1 NM_022136.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

SAMSN1 (HGNC:10528): (SAM domain, SH3 domain and nuclear localization signals 1) SAMSN1 is a member of a novel gene family of putative adaptors and scaffold proteins containing SH3 and SAM (sterile alpha motif) domains (Claudio et al., 2001 [PubMed 11536050]).[supplied by OMIM, Mar 2008]

LOC124905053 (HGNC:):

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=0.1901162).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022136.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMSN1	NM_022136.5	MANE Select	c.344C>G	p.Thr115Arg	missense	Exon 4 of 8	NP_071419.3
	SAMSN1	NM_001395858.1		c.1328C>G	p.Thr443Arg	missense	Exon 14 of 18	NP_001382787.1
	SAMSN1	NM_001395857.1		c.1232C>G	p.Thr411Arg	missense	Exon 12 of 16	NP_001382786.1	A0A2R8Y4K8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMSN1	ENST00000400566.6	TSL:1 MANE Select	c.344C>G	p.Thr115Arg	missense	Exon 4 of 8	ENSP00000383411.2	Q9NSI8-1
	SAMSN1	ENST00000285670.7	TSL:1	c.548C>G	p.Thr183Arg	missense	Exon 5 of 9	ENSP00000285670.2	Q9NSI8-3
	SAMSN1	ENST00000619120.4	TSL:1	c.137C>G	p.Thr46Arg	missense	Exon 5 of 9	ENSP00000480850.1	S6FRS6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.26
Sift	Benign	0.64	T
Sift4G	Benign	0.54	T
Polyphen		0.84	P
Vest4		0.26
MutPred		0.19		Loss of phosphorylation at T115 (P = 0.0499)
MVP		0.66
MPC		0.19
ClinPred		0.55	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.41
Mutation Taster		=77/23	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: chr21-15884830; COSMIC: COSV53472434;