17-50113046-G-C

Variant names:

• chr17-50113046-G-C
• rs1307128404
• NM_001257359.2:c.1101C>G

Variant summary

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

The NM_001257359.2(SAMD14):​c.1101C>G​(p.Ser367Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,336 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: 6.9e-7 (0 hom.)
• Consequence: SAMD14 NM_001257359.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.607
• 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.1101C>G	p.Ser367Arg	missense splice_region	Exon 10 of 10	NP_001244288.1	Q8IZD0-1
	SAMD14	NM_174920.4		c.1185C>G	p.Ser395Arg	missense splice_region	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.1101C>G	p.Ser367Arg	missense splice_region	Exon 10 of 10	ENSP00000329144.4	Q8IZD0-1
	SAMD14	ENST00000503131.1	TSL:1	c.1185C>G	p.Ser395Arg	missense splice_region	Exon 11 of 11	ENSP00000424474.1	Q8IZD0-2
	SAMD14	ENST00000285206.12	TSL:1	c.1137C>G	p.Ser379Arg	missense splice_region	Exon 9 of 9	ENSP00000285206.8	J3KN99

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459336 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726076

African (AFR) AF: 0.00 AC: 0 AN: 33474

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51010

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60364

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	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.037
Eigen_PC	Benign	0.082
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.61
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.037	D
Polyphen		0.80	P
Vest4		0.21
MutPred		0.41		Gain of helix (P = 0.0078)
MVP		0.87
MPC		0.64
ClinPred		0.95	D
GERP RS		3.1
Varity_R		0.55
gMVP		0.43
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1307128404; hg19: chr17-48190410;