Genetic Variant SPAG16:c.1071-4G>T (chr2-213862481-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024532.5(SPAG16):c.1071-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,612,676 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 211 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 193 hom. )

Consequence

SPAG16
NM_024532.5 splice_region, intron

Scores

Splicing: ADA: 0.00005070

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.789

Publications

2 publications found

Variant links:

Genes affected

SPAG16 (HGNC:23225): (sperm associated antigen 16) Cilia and flagella are comprised of a microtubular backbone, the axoneme, which is organized by the basal body and surrounded by plasma membrane. SPAG16 encodes 2 major proteins that associate with the axoneme of sperm tail and the nucleus of postmeiotic germ cells, respectively (Zhang et al., 2007 [PubMed 17699735]).[supplied by OMIM, Jul 2008]

SPAG16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-213862481-G-T is Benign according to our data. Variant chr2-213862481-G-T is described in ClinVar as Benign. ClinVar VariationId is 767850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG16	NM_024532.5 link	c.1071-4G>T		splice_region_variant, intron_variant	Intron 10 of 15	ENST00000331683.10	NP_078808.3	Q8N0X2-1Q4G1A2B4DYB5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPAG16	ENST00000331683.10 link	c.1071-4G>T	splice_region_variant, intron_variant	Intron 10 of 15	1	NM_024532.5	ENSP00000332592.5	Q8N0X2-1
SPAG16	ENST00000406979.6 link	n.*1072-4G>T	splice_region_variant, intron_variant	Intron 12 of 17	1		ENSP00000385496.2	F8WB32
SPAG16	ENST00000451561.1 link	c.129-4G>T	splice_region_variant, intron_variant	Intron 1 of 5	3		ENSP00000416600.1	H0Y811
SPAG16	ENST00000452556.5 link	n.*637-4G>T	splice_region_variant, intron_variant	Intron 8 of 13	2		ENSP00000398926.1	F8WBQ0

Frequencies

GnomAD3 genomes

AF:

0.0276

AC:

4199

AN:

151912

Hom.:

209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0960

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00852

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000568

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.0230

GnomAD2 exomes

AF:

0.00766

AC:

1920

AN:

250640

AF XY:

0.00552

show subpopulations

Gnomad AFR exome

AF:

0.0997

Gnomad AMR exome

AF:

0.00516

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.000557

Gnomad OTH exome

AF:

0.00540

GnomAD4 exome

AF:

0.00314

AC:

4589

AN:

1460646

Hom.:

193

Cov.:

AF XY:

0.00277

AC XY:

2011

AN XY:

726492

show subpopulations

African (AFR)

AF:

0.101

AC:

3384

AN:

33456

American (AMR)

AF:

0.00548

AC:

245

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.000345

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.000209

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.000618

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00975

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.000340

AC:

378

AN:

1111106

Other (OTH)

AF:

0.00772

AC:

466

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

209

418

626

835

1044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.0277

AC:

4211

AN:

152030

Hom.:

211

Cov.:

AF XY:

0.0268

AC XY:

1994

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0960

AC:

3978

AN:

41440

American (AMR)

AF:

0.00851

AC:

130

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.000568

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

67994

Other (OTH)

AF:

0.0227

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

197

394

591

788

985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0211

Hom.:

132

Bravo

AF:

0.0318

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000656

EpiControl

AF:

0.000832

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 15, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.29

(source)

DANN

Benign

0.38

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000051

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.050

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over