2-213375022-G-T

Variant names:

• chr2-213375022-G-T
• rs752778146
• NM_024532.5:c.845G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024532.5(SPAG16):​c.845G>T​(p.Arg282Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R282H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04338798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024532.5. 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
	SPAG16	NM_024532.5	MANE Select	c.845G>T	p.Arg282Leu	missense	Exon 9 of 16	NP_078808.3
	SPAG16	NR_047659.2		n.1040G>T		non_coding_transcript_exon	Exon 11 of 18
	SPAG16	NR_047660.2		n.746G>T		non_coding_transcript_exon	Exon 8 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.845G>T	p.Arg282Leu	missense	Exon 9 of 16	ENSP00000332592.5	Q8N0X2-1
	SPAG16	ENST00000447990.1	TSL:1	c.845G>T	p.Arg282Leu	missense	Exon 9 of 10	ENSP00000400847.1	E7EWV3
	SPAG16	ENST00000406979.6	TSL:1	n.*846G>T		non_coding_transcript_exon	Exon 11 of 18	ENSP00000385496.2	F8WB32

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451544 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722310

African (AFR) AF: 0.00 AC: 0 AN: 32772

American (AMR) AF: 0.00 AC: 0 AN: 42822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39396

South Asian (SAS) AF: 0.00 AC: 0 AN: 84446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107184

Other (OTH) AF: 0.00 AC: 0 AN: 59962

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.30
DANN	Benign	0.43
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.35
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.070
Sift	Benign	0.66	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.34
MutPred		0.36		Loss of sheet (P = 0.0126)
MVP		0.23
MPC		0.024
ClinPred		0.022	T
GERP RS		-4.4
Varity_R		0.044
gMVP		0.20
Mutation Taster		=98/2	polymorphism

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: rs752778146; hg19: chr2-214239746;