17-50112942-C-A

Variant names:

• chr17-50112942-C-A
• rs369309802
• NM_001257359.2:c.1205G>T

Variant summary

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

The NM_001257359.2(SAMD14):​c.1205G>T​(p.Arg402Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R402Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SAMD14 NM_001257359.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21579275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD14	NM_001257359.2	c.1205G>T	p.Arg402Leu	missense_variant	Exon 10 of 10	ENST00000330175.9	NP_001244288.1
SAMD14	NM_174920.4	c.1289G>T	p.Arg430Leu	missense_variant	Exon 11 of 11		NP_777580.1
SAMD14	XM_017024322.3	c.1454G>T	p.Arg485Leu	missense_variant	Exon 9 of 9		XP_016879811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD14	ENST00000330175.9	c.1205G>T	p.Arg402Leu	missense_variant	Exon 10 of 10	1	NM_001257359.2	ENSP00000329144.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457344 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725262

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

American (AMR) AF: 0.00 AC: 0 AN: 44706

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: 49046

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111920

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.0027	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.030
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.
PhyloP100		2.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.65	P;.;B
Vest4		0.41
MutPred		0.18		Loss of methylation at K399 (P = 0.1971);.;.;
MVP		0.50
MPC		0.19
ClinPred		0.96	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.18
gMVP		0.51

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: rs369309802; hg19: chr17-48190306;