NM_001040159.2:c.1257A>C

Variant names:

• chr4-166734966-T-G
• NM_001040159.2:c.1257A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040159.2(SPOCK3):​c.1257A>C​(p.Glu419Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: SPOCK3 NM_001040159.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87
• Publications: 0 publications found

Genes affected

SPOCK3 (HGNC:13565): (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 3) This gene encodes a member of a novel family of calcium-binding proteoglycan proteins that contain thyroglobulin type-1 and Kazal-like domains. The encoded protein and may play a role in adult T-cell leukemia by inhibiting the activity of membrane-type matrix metalloproteinases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

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=0.13761988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040159.2. 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
	SPOCK3	NM_001040159.2	MANE Select	c.1257A>C	p.Glu419Asp	missense	Exon 11 of 11	NP_001035249.1	Q9BQ16-1
	SPOCK3	NM_016950.3		c.1266A>C	p.Glu422Asp	missense	Exon 12 of 12	NP_058646.2	Q9BQ16-3
	SPOCK3	NM_001430594.1		c.1257A>C	p.Glu419Asp	missense	Exon 10 of 10	NP_001417523.1	Q9BQ16-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCK3	ENST00000357545.9	TSL:1 MANE Select	c.1257A>C	p.Glu419Asp	missense	Exon 11 of 11	ENSP00000350153.4	Q9BQ16-1
	SPOCK3	ENST00000502330.5	TSL:1	c.1266A>C	p.Glu422Asp	missense	Exon 12 of 12	ENSP00000423606.1	Q9BQ16-3
	SPOCK3	ENST00000357154.7	TSL:5	c.1266A>C	p.Glu422Asp	missense	Exon 12 of 12	ENSP00000349677.3	Q9BQ16-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 32

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	0.095
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.12	N
PhyloP100		1.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.48	T
Polyphen		0.87	P
Vest4		0.098
MutPred		0.058		Loss of helix (P = 0.2662)
MVP		0.84
MPC		0.15
ClinPred		0.23	T
GERP RS		1.3
Varity_R		0.22
gMVP		0.066
Mutation Taster		=91/9	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

hg19: chr4-167656117;