rs766542274

Variant names:

• chr19-367203-C-A
• NM_016585.5:c.775G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-367203-C-A
• chr19-367203-C-T

Variant summary

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

The NM_016585.5(SPMAP2):​c.775G>T​(p.Ala259Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A259T) 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: 1.07

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

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
SPMAP2	NM_016585.5	c.775G>T	p.Ala259Ser	missense_variant	Exon 7 of 8	ENST00000342640.9	NP_057669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THEG	ENST00000342640.9	c.775G>T	p.Ala259Ser	missense_variant	Exon 7 of 8	1	NM_016585.5	ENSP00000340088.3
THEG	ENST00000346878.3	c.703G>T	p.Ala235Ser	missense_variant	Exon 6 of 7	2		ENSP00000264820.3
THEG	ENST00000530711.3	c.108G>T	p.Gln36His	missense_variant	Exon 2 of 3	3		ENSP00000475782.2
THEG	ENST00000528213.1	n.582G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452634 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722572

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	2.9	.;M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.62
MutPred		0.19		.;Gain of phosphorylation at A259 (P = 0.0197);
MVP		0.38
MPC		0.31
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.40
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-367203;