19-362276-C-T

Variant names:

• chr19-362276-C-T
• rs1211993267
• NM_016585.5:c.1064G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016585.5(SPMAP2):​c.1064G>A​(p.Arg355His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,445,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R355C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: SPMAP2 NM_016585.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.97
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022862822).
• BP6: Variant 19-362276-C-T is Benign according to our data. Variant chr19-362276-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3235639.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1064G>A	p.Arg355His	missense	Exon 8 of 8	NP_057669.1	Q9P2T0-1
	SPMAP2	NM_199202.3		c.992G>A	p.Arg331His	missense	Exon 7 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.1064G>A	p.Arg355His	missense	Exon 8 of 8	ENSP00000340088.3	Q9P2T0-1
	SPMAP2	ENST00000346878.3	TSL:2	c.992G>A	p.Arg331His	missense	Exon 7 of 7	ENSP00000264820.3	Q9P2T0-2
	SPMAP2	ENST00000530711.3	TSL:3	c.397G>A	p.Val133Ile	missense	Exon 3 of 3	ENSP00000475782.2	U3KQD4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 243072 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000692 AC: 10 AN: 1445764 Hom.: 0 Cov.: 30 AF XY: 0.00000697 AC XY: 5 AN XY: 717270

African (AFR) AF: 0.0000301 AC: 1 AN: 33222

American (AMR) AF: 0.00 AC: 0 AN: 43104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25746

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39248

South Asian (SAS) AF: 0.00 AC: 0 AN: 82940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000635 AC: 7 AN: 1102778

Other (OTH) AF: 0.0000167 AC: 1 AN: 59786

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0010
DANN	Benign	0.80
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00044	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-8.0
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.030
Sift	Benign	0.35	T
Sift4G	Benign	0.44	T
Polyphen		0.0010	B
Vest4		0.074
MutPred		0.20		Loss of MoRF binding (P = 0.0454)
MVP		0.030
MPC		0.056
ClinPred		0.088	T
GERP RS		-8.1
Varity_R		0.018
gMVP		0.31
Mutation Taster		=95/5	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: rs1211993267; hg19: chr19-362276; COSMIC: COSV61073691; COSMIC: COSV61073691;