21-14512509-G-C

Position:

• chr21-14512509-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1901162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMSN1	NM_022136.5	c.344C>G	p.Thr115Arg	missense_variant	4/8	ENST00000400566.6	NP_071419.3
LOC124905053	XR_007067925.1	n.340-25337G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMSN1	ENST00000400566.6	c.344C>G	p.Thr115Arg	missense_variant	4/8	1	NM_022136.5	ENSP00000383411	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.344C>G (p.T115R) alteration is located in exon 4 (coding exon 4) of the SAMSN1 gene. This alteration results from a C to G substitution at nucleotide position 344, causing the threonine (T) at amino acid position 115 to be replaced by an arginine (R). 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	0.082
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.;T;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M;.;.;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N;.;.;N
REVEL	Benign	0.26
Sift	Benign	0.64	T;.;.;T
Sift4G	Benign	0.54	T;.;T;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-15884830; COSMIC: COSV53472434;