Genetic Variant NM_016585.5:c.1064G>A (chr19-362276-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.97

Publications

3 publications found

Variant links:

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]

SPMAP2 links:

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ACMG classification

Classification was made for transcript

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

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.:

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

243072

AF XY:

0.0000152

show subpopulations

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:

AN:

1445764

Hom.:

Cov.:

AF XY:

0.00000697

AC XY:

AN XY:

717270

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33222

American (AMR)

AF:

0.00

AC:

AN:

43104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25746

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39248

South Asian (SAS)

AF:

0.00

AC:

AN:

82940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00000635

AC:

AN:

1102778

Other (OTH)

AF:

0.0000167

AC:

AN:

59786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0010

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.035

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00044

LIST_S2

Benign

0.42

M_CAP

Benign

0.0029

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.69

PhyloP100

-8.0

PrimateAI

Benign

0.21

PROVEAN

Benign

1.8

REVEL

Benign

0.030

Sift

Benign

0.35

Sift4G

Benign

0.44

Polyphen

0.0010

Vest4

0.074

MutPred

0.20

Loss of MoRF binding (P = 0.0454)

MVP

0.030

MPC

0.056

ClinPred

0.088

GERP RS

-8.1

Varity_R

0.018

gMVP

0.31

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over