2-168873630-G-T

Position:

• chr2-168873630-G-T

Variant summary

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

The NM_020675.4(SPC25):​c.505C>A​(p.Pro169Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPC25 NM_020675.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49

Genes affected

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPC25	NM_020675.4	c.505C>A	p.Pro169Thr	missense_variant	6/7	ENST00000282074.7
SPC25	XM_011511516.3	c.505C>A	p.Pro169Thr	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPC25	ENST00000282074.7	c.505C>A	p.Pro169Thr	missense_variant	6/7	1	NM_020675.4	P1
SPC25	ENST00000479309.6	n.374C>A		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Nov 30, 2021

The c.505C>A (p.P169T) alteration is located in exon 6 (coding exon 5) of the SPC25 gene. This alteration results from a C to A substitution at nucleotide position 505, causing the proline (P) at amino acid position 169 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.18
Sift	Benign	0.091	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.48		Loss of glycosylation at P169 (P = 0.0857);
MVP		0.76
MPC		0.41
ClinPred		0.86	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.37

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: chr2-169730140;