chr17-50113973-C-A

Variant names:

• chr17-50113973-C-A
• rs564137587
• NM_001257359.2:c.1049G>T

Variant summary

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

The NM_001257359.2(SAMD14):​c.1049G>T​(p.Arg350Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R350Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SAMD14 NM_001257359.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD14	NM_001257359.2	c.1049G>T	p.Arg350Leu	missense_variant	Exon 9 of 10	ENST00000330175.9	NP_001244288.1
SAMD14	NM_174920.4	c.1133G>T	p.Arg378Leu	missense_variant	Exon 10 of 11		NP_777580.1
SAMD14	XM_017024322.3	c.1298G>T	p.Arg433Leu	missense_variant	Exon 8 of 9		XP_016879811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD14	ENST00000330175.9	c.1049G>T	p.Arg350Leu	missense_variant	Exon 9 of 10	1	NM_001257359.2	ENSP00000329144.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461432 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727044

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.78	N;.;.
PhyloP100		0.87
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.98	D;.;P
Vest4		0.41
MutPred		0.45		Loss of disorder (P = 0.106);.;.;
MVP		0.88
MPC		0.39
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.27
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs564137587; hg19: chr17-48191337;