19-367082-C-A

Variant names:

• chr19-367082-C-A
• rs780064961
• NM_016585.5:c.896G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016585.5(SPMAP2):​c.896G>T​(p.Arg299Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R299C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPMAP2 NM_016585.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 5 publications found

Genes affected

SPMAP2 (HGNC:13706): (sperm microtubule associated protein 2) This gene is specifically expressed in the nucleus of haploid male germ cells. The orthologous gene in mice encodes a protein that may play a role in protein assembly through interactions with T-complex protein 1 subunit epsilon. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24267492).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016585.5. 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
	SPMAP2	NM_016585.5	MANE Select	c.896G>T	p.Arg299Leu	missense	Exon 7 of 8	NP_057669.1	Q9P2T0-1
	SPMAP2	NM_199202.3		c.824G>T	p.Arg275Leu	missense	Exon 6 of 7	NP_954672.1	Q9P2T0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPMAP2	ENST00000342640.9	TSL:1 MANE Select	c.896G>T	p.Arg299Leu	missense	Exon 7 of 8	ENSP00000340088.3	Q9P2T0-1
	SPMAP2	ENST00000346878.3	TSL:2	c.824G>T	p.Arg275Leu	missense	Exon 6 of 7	ENSP00000264820.3	Q9P2T0-2
	SPMAP2	ENST00000530711.3	TSL:3	c.229G>T	p.Ala77Ser	missense	Exon 2 of 3	ENSP00000475782.2	U3KQD4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460306 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726464

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 85858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111448

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.44	T
PhyloP100		1.6
REVEL	Benign	0.085
Sift4G	Benign	0.42	T
Vest4		0.30
MutPred		0.27		Loss of sheet (P = 0.0181)
MVP		0.072
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.85
Mutation Taster		=67/33	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: rs780064961; hg19: chr19-367082;