5-169591070-C-G

Variant names:

• chr5-169591070-C-G
• rs1755254270
• NM_017785.5:c.182C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017785.5(SPDL1):​c.182C>G​(p.Thr61Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPDL1 NM_017785.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

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]

SPDL1 Gene-Disease associations (from GenCC):

• microcephaly

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035434365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017785.5. 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
	SPDL1	NM_017785.5	MANE Select	c.182C>G	p.Thr61Ser	missense	Exon 3 of 12	NP_060255.3
	SPDL1	NM_001329639.2		c.182C>G	p.Thr61Ser	missense	Exon 3 of 11	NP_001316568.1
	SPDL1	NM_001329640.2		c.182C>G	p.Thr61Ser	missense	Exon 3 of 11	NP_001316569.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDL1	ENST00000265295.9	TSL:1 MANE Select	c.182C>G	p.Thr61Ser	missense	Exon 3 of 12	ENSP00000265295.4	Q96EA4-1
	SPDL1	ENST00000507232.5	TSL:1	n.97C>G		non_coding_transcript_exon	Exon 3 of 11	ENSP00000425357.1	D6RDK5
	SPDL1	ENST00000510751.5	TSL:1	n.339C>G		non_coding_transcript_exon	Exon 3 of 8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.088
Sift	Benign	0.89	T
Sift4G	Benign	0.89	T
Polyphen		0.037	B
Vest4		0.098
MutPred		0.078		Gain of phosphorylation at T61 (P = 0.1239)
MVP		0.19
MPC		0.032
ClinPred		0.44	T
GERP RS		4.5
PromoterAI		0.0049	Neutral
Varity_R		0.065
gMVP		0.031
Mutation Taster		=89/11	polymorphism

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: rs1755254270; hg19: chr5-169018074;