7-149777304-A-C

Variant names:

• chr7-149777304-A-C
• ENST00000378016.5:n.437A>C

Variant summary

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

The NR_163594.1(SSPOP):​n.437A>C variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SSPOP NR_163594.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0960

Genes affected

SSPOP (HGNC:21998): (SCO-spondin, pseudogene) Predicted to enable peptidase inhibitor activity. Predicted to be involved in several processes, including cell adhesion; negative regulation of catalytic activity; and regulation of peptidase activity. Predicted to be located in cytoplasm. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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=0.039928257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSPOP	NR_163594.1	n.437A>C		non_coding_transcript_exon_variant	Exon 4 of 103

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSPOP	ENST00000378016.5	n.437A>C		non_coding_transcript_exon_variant	Exon 4 of 103	5
SSPOP	ENST00000486824.3	n.94+776A>C		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.437A>C (p.Q146P) alteration is located in exon 4 (coding exon 4) of the SSPO gene. This alteration results from a A to C substitution at nucleotide position 437, causing the glutamine (Q) at amino acid position 146 to be replaced by a proline (P). 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	0.094
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	7.0
DANN	Benign	0.73
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.040	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.22	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.022	B
Vest4		0.25
MVP		0.12
GERP RS		-0.23
Varity_R		0.14
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-149474393;