Genetic Variant NM_024532.5:c.509A>G (chr2-213317329-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024532.5(SPAG16):c.509A>G(p.Asp170Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SPAG16
NM_024532.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG16	NM_024532.5 link	c.509A>G	p.Asp170Gly	missense_variant	Exon 5 of 16	ENST00000331683.10	NP_078808.3	Q8N0X2-1Q4G1A2B4DYB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG16	ENST00000331683.10 link	c.509A>G	p.Asp170Gly	missense_variant	Exon 5 of 16	1	NM_024532.5	ENSP00000332592.5		Q8N0X2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458414

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725598

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.509A>G (p.D170G) alteration is located in exon 5 (coding exon 5) of the SPAG16 gene. This alteration results from a A to G substitution at nucleotide position 509, causing the aspartic acid (D) at amino acid position 170 to be replaced by a glycine (G). 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

0.21

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;D;.;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;D;D;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.51

D;D;D;D;D

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.3

.;M;M;.;.

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.2

D;D;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.010

D;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

0.55, 0.87

.;P;P;.;.

Vest4

0.40, 0.44, 0.57, 0.63

MutPred

0.49

Loss of stability (P = 0.0164);Loss of stability (P = 0.0164);Loss of stability (P = 0.0164);.;Loss of stability (P = 0.0164);

MVP

0.70

MPC

0.063

ClinPred

0.99

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.50

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over