Genetic Variant SPANXC:p.Glu65Gly (chrX-141241617-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022661.4(SPANXC):c.194A>G(p.Glu65Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 5 hom., 25 hem., cov: 9)

Exomes 𝑓: 0.00024 ( 1 hom. 42 hem. )

Failed GnomAD Quality Control

Consequence

SPANXC
NM_022661.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.70

Publications

0 publications found

Variant links:

Genes affected

SPANXC (HGNC:14331): (SPANX family member C) Temporally regulated transcription and translation of several testis-specific genes is required to initiate the series of molecular and morphological changes in the male germ cell lineage necessary for the formation of mature spermatozoa. This gene is a member of the SPANX family, which is located in a gene cluster on chromosome X. The SPANX genes encode differentially expressed testis-specific proteins that localize to various subcellular compartments. This particular gene encodes a protein that localizes to the nucleus and is expressed in highly metastatic cell lines, making the protein a potential diagnostic and prognostic marker. The protein belongs to a family of cancer/testis antigens and represents a potential target for cancer immunotherapy. [provided by RefSeq, Jul 2008]

SPANXC links:

SPANXA2-OT1 (HGNC:31683): (SPANXA2 overlapping transcript 1)

SPANXA2-OT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0109600425).

BP6

Variant X-141241617-T-C is Benign according to our data. Variant chrX-141241617-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2661547.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022661.4. 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
	SPANXC	NM_022661.4	MANE Select	c.194A>G	p.Glu65Gly	missense	Exon 2 of 2	NP_073152.2	Q9NY87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPANXC	ENST00000358993.3	TSL:1 MANE Select	c.194A>G	p.Glu65Gly	missense	Exon 2 of 2	ENSP00000351884.2	Q9NY87
	SPANXA2-OT1	ENST00000662492.1		n.102+53780T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

148

AN:

62099

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00703

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.0000350

Gnomad OTH

AF:

0.00135

GnomAD2 exomes

AF:

0.000124

AC:

AN:

177640

AF XY:

0.0000477

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000379

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000242

AC:

259

AN:

1070805

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

343339

show subpopulations

African (AFR)

AF:

0.00547

AC:

141

AN:

25790

American (AMR)

AF:

0.000461

AC:

AN:

34679

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18802

East Asian (EAS)

AF:

0.00

AC:

AN:

27724

South Asian (SAS)

AF:

0.00

AC:

AN:

53519

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3352

European-Non Finnish (NFE)

AF:

0.0000996

AC:

AN:

823222

Other (OTH)

AF:

0.000448

AC:

AN:

44653

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.00238

AC:

148

AN:

62112

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

AN XY:

11486

show subpopulations

African (AFR)

AF:

0.00702

AC:

140

AN:

19951

American (AMR)

AF:

0.00110

AC:

AN:

5434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1511

East Asian (EAS)

AF:

0.00

AC:

AN:

1366

South Asian (SAS)

AF:

0.00

AC:

AN:

1099

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2841

Middle Eastern (MID)

AF:

0.00

AC:

AN:

107

European-Non Finnish (NFE)

AF:

0.0000350

AC:

AN:

28579

Other (OTH)

AF:

0.00134

AC:

AN:

744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00160

Hom.:

ExAC

AF:

0.000227

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.4

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.00036

LIST_S2

Benign

0.32

M_CAP

Benign

0.0015

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.96

PhyloP100

-2.7

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.5

REVEL

Benign

0.023

Sift

Benign

0.25

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.17

MVP

0.10

MPC

1.9

ClinPred

0.20

Varity_R

0.13

gMVP

0.0039

Mutation Taster

=100/0

polymorphism

(source)

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

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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