5-169593430-A-G

Position:

• chr5-169593430-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017785.5(SPDL1):​c.413A>G​(p.Lys138Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPDL1 NM_017785.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69

Genes affected

SPDL1 (HGNC:26010): (spindle apparatus coiled-coil protein 1) This gene encodes a coiled-coil domain-containing protein that functions in mitotic spindle formation and chromosome segregation. The encoded protein plays a role in coordinating microtubule attachment by promoting recruitment of dynein proteins, and in mitotic checkpoint signaling. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11136243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPDL1	NM_017785.5	c.413A>G	p.Lys138Arg	missense_variant	4/12	ENST00000265295.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPDL1	ENST00000265295.9	c.413A>G	p.Lys138Arg	missense_variant	4/12	1	NM_017785.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2023

The c.413A>G (p.K138R) alteration is located in exon 4 (coding exon 3) of the SPDL1 gene. This alteration results from a A to G substitution at nucleotide position 413, causing the lysine (K) at amino acid position 138 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0069	T;T;T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.0032
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.62	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;.;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.19	T;T;T;T
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.49	P;.;.;.
Vest4		0.33
MutPred		0.14		Loss of ubiquitination at K138 (P = 0.0034);Loss of ubiquitination at K138 (P = 0.0034);Loss of ubiquitination at K138 (P = 0.0034);Loss of ubiquitination at K138 (P = 0.0034);
MVP		0.50
MPC		0.050
ClinPred		0.32	T
GERP RS		4.6
Varity_R		0.035
gMVP		0.019

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-169020434;