rs559833981

Variant names:

• chr5-169588463-C-G
• NM_017785.5:c.47C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-169588463-C-G
• chr5-169588463-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017785.5(SPDL1):​c.47C>G​(p.Ala16Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. A16V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPDL1 NM_017785.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031577736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPDL1	NM_017785.5	c.47C>G	p.Ala16Gly	missense_variant	Exon 2 of 12	ENST00000265295.9	NP_060255.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPDL1	ENST00000265295.9	c.47C>G	p.Ala16Gly	missense_variant	Exon 2 of 12	1	NM_017785.5	ENSP00000265295.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461154 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726846

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0089	T;T;T;.;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.81	T;T;T;T;T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.032	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.;.;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.5	N;D;D;.;N;N;N
REVEL	Benign	0.091
Sift	Benign	0.26	T;T;T;.;T;T;T
Sift4G	Benign	0.24	T;T;T;D;T;T;T
Polyphen		0.0010	B;.;.;.;.;.;.
Vest4		0.18
MutPred		0.13		Loss of stability (P = 0.1029);Loss of stability (P = 0.1029);Loss of stability (P = 0.1029);Loss of stability (P = 0.1029);Loss of stability (P = 0.1029);Loss of stability (P = 0.1029);Loss of stability (P = 0.1029);
MVP		0.067
MPC		0.072
ClinPred		0.069	T
GERP RS		-5.3
Varity_R		0.037
gMVP		0.056

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: chr5-169015467;