7-149777232-G-A

Variant names:

• chr7-149777232-G-A
• rs894793359
• ENST00000378016.5:n.365G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NR_163594.1(SSPOP):​n.365G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000171 in 1,169,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SSPOP NR_163594.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32
• Publications: 0 publications found

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]

ENSG00000293556 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.758

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_163594.1. 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
	SSPOP	NR_163594.1		n.365G>A		non_coding_transcript_exon	Exon 4 of 103

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSPOP	ENST00000378016.5	TSL:5	n.365G>A		non_coding_transcript_exon	Exon 4 of 103
	ENSG00000293556	ENST00000486824.3	TSL:4	n.94+704G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000171 AC: 2 AN: 1169036 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 575238

African (AFR) AF: 0.00 AC: 0 AN: 25004

American (AMR) AF: 0.00 AC: 0 AN: 30782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16104

East Asian (EAS) AF: 0.00 AC: 0 AN: 13970

South Asian (SAS) AF: 0.00 AC: 0 AN: 77358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4148

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 931366

Other (OTH) AF: 0.0000236 AC: 1 AN: 42310

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	18
DANN	Benign	0.74
DEOGEN2	Benign	0.24	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.53	T
MetaRNN	Pathogenic	0.76	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.3
PrimateAI	Uncertain	0.68	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.80
MVP		0.19
GERP RS		4.6
Varity_R		0.66
gMVP		0.94

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: rs894793359; hg19: chr7-149474321;