Genetic Variant SSPOP:n.234A>T (chr7-149776935-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NR_163594.1(SSPOP):n.234A>T variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000559 in 1,366,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

SSPOP
NR_163594.1 splice_region, non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.308

Publications

1 publications found

Variant links:

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]

SSPOP links:

ENSG00000293556 (HGNC:):

ENSG00000293556 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1498256).

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.234A>T		splice_region non_coding_transcript_exon	Exon 3 of 103

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSPOP	ENST00000378016.5	TSL:5	n.234A>T		splice_region non_coding_transcript_exon	Exon 3 of 103
	ENSG00000293556	ENST00000486824.3	TSL:4	n.94+407A>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000343

AC:

AN:

247660

AF XY:

0.000386

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000563

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000600

AC:

729

AN:

1214420

Hom.:

Cov.:

AF XY:

0.000557

AC XY:

335

AN XY:

601852

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26300

American (AMR)

AF:

0.000403

AC:

AN:

37262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16882

East Asian (EAS)

AF:

0.00

AC:

AN:

16806

South Asian (SAS)

AF:

0.000168

AC:

AN:

83214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31758

Middle Eastern (MID)

AF:

0.000447

AC:

AN:

4472

European-Non Finnish (NFE)

AF:

0.000711

AC:

678

AN:

953752

Other (OTH)

AF:

0.000455

AC:

AN:

43974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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

AF:

0.000230

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41314

American (AMR)

AF:

0.000131

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

67974

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000490

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000485

AC:

ExAC

AF:

0.000323

AC:

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

Pathogenic

0.84

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.0

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.097

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.65

MetaRNN

Benign

0.15

MutationAssessor

Uncertain

2.3

PhyloP100

0.31

PrimateAI

Uncertain

0.49

Sift4G

Pathogenic

0.0010

Polyphen

0.96

Vest4

0.46

MVP

0.11

GERP RS

-0.018

Varity_R

0.057

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over