Genetic Variant NM_017785.5:c.550G>A (chr5-169594163-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017785.5(SPDL1):c.550G>A(p.Val184Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,154 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SPDL1
NM_017785.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.177

Publications

0 publications found

Variant links:

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

SPDL1 links:

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ACMG classification

Classification was made for transcript

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=0.11798385).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SPDL1	NM_017785.5	MANE Select	c.550G>A	p.Val184Met	missense	Exon 5 of 12	NP_060255.3
SPDL1	NM_001329639.2		c.550G>A	p.Val184Met	missense	Exon 5 of 11	NP_001316568.1
SPDL1	NM_001329640.2		c.550G>A	p.Val184Met	missense	Exon 5 of 11	NP_001316569.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPDL1	ENST00000265295.9	TSL:1 MANE Select	c.550G>A	p.Val184Met	missense	Exon 5 of 12	ENSP00000265295.4	Q96EA4-1
SPDL1	ENST00000507232.5	TSL:1	n.*330G>A		non_coding_transcript_exon	Exon 5 of 11	ENSP00000425357.1	D6RDK5
SPDL1	ENST00000510751.5	TSL:1	n.707G>A		non_coding_transcript_exon	Exon 5 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453154

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722590

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32838

American (AMR)

AF:

0.00

AC:

AN:

42298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25706

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

83820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109762

Other (OTH)

AF:

0.00

AC:

AN:

60028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.058

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.81

M_CAP

Benign

0.016

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

PhyloP100

0.18

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.66

REVEL

Benign

0.14

Sift

Uncertain

0.016

Sift4G

Benign

0.098

Polyphen

0.96

Vest4

0.24

MutPred

0.085

Gain of catalytic residue at V184 (P = 0.1277)

MVP

0.62

MPC

0.044

ClinPred

0.19

GERP RS

2.9

Varity_R

0.035

gMVP

0.040

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over