chr21-14516908-G-C

Variant names:

• chr21-14516908-G-C
• rs200178567
• NM_022136.5:c.263C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022136.5(SAMSN1):​c.263C>G​(p.Ala88Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,148 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SAMSN1 NM_022136.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.45

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMSN1	NM_022136.5	c.263C>G	p.Ala88Gly	missense_variant	Exon 3 of 8	ENST00000400566.6	NP_071419.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMSN1	ENST00000400566.6	c.263C>G	p.Ala88Gly	missense_variant	Exon 3 of 8	1	NM_022136.5	ENSP00000383411.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000410 AC: 1 AN: 244002 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132324

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456148 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724252

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;.;T;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.7	M;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.9	D;.;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.0090	D;.;.;D
Sift4G	Uncertain	0.049	D;.;D;D
Polyphen		0.98	D;.;.;.
Vest4		0.40
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0479);.;.;.;
MVP		0.87
MPC		0.57
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs200178567; hg19: chr21-15889229;