chr17-50112955-C-T

Variant names:

• chr17-50112955-C-T
• rs984542545
• NM_001257359.2:c.1192G>A

Variant summary

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

The NM_001257359.2(SAMD14):​c.1192G>A​(p.Glu398Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,458,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SAMD14 NM_001257359.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13
• Publications: 0 publications found

Genes affected

SAMD14 (HGNC:27312): (sterile alpha motif domain containing 14) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament organization; calcium-mediated signaling; and neuron projection development. Predicted to be active in several cellular components, including actin cytoskeleton; dendrite; and postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257359.2. 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
	SAMD14	NM_001257359.2	MANE Select	c.1192G>A	p.Glu398Lys	missense	Exon 10 of 10	NP_001244288.1	Q8IZD0-1
	SAMD14	NM_174920.4		c.1276G>A	p.Glu426Lys	missense	Exon 11 of 11	NP_777580.1	Q8IZD0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD14	ENST00000330175.9	TSL:1 MANE Select	c.1192G>A	p.Glu398Lys	missense	Exon 10 of 10	ENSP00000329144.4	Q8IZD0-1
	SAMD14	ENST00000503131.1	TSL:1	c.1276G>A	p.Glu426Lys	missense	Exon 11 of 11	ENSP00000424474.1	Q8IZD0-2
	SAMD14	ENST00000285206.12	TSL:1	c.1228G>A	p.Glu410Lys	missense	Exon 9 of 9	ENSP00000285206.8	J3KN99

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458680 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725880

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.075	T
Polyphen		0.99	D
Vest4		0.47
MutPred		0.26		Gain of methylation at E398 (P = 0.0184)
MVP		0.78
MPC		0.17
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.53
gMVP		0.46
Mutation Taster		=34/66	disease causing

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

dbSNP: rs984542545; hg19: chr17-48190319;