2-88529081-C-A

Position:

• chr2-88529081-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152670.3(SPMIP9):​c.150C>A​(p.Asp50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPMIP9 NM_152670.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.697

Genes affected

SPMIP9 (HGNC:26341): (sperm microtubule inner protein 9) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042503625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPMIP9	NM_152670.3	c.150C>A	p.Asp50Glu	missense_variant	4/4	ENST00000303254.4	NP_689883.1
SPMIP9	XM_005264188.4	c.150C>A	p.Asp50Glu	missense_variant	4/4		XP_005264245.3
SPMIP9	XM_011532691.2	c.150C>A	p.Asp50Glu	missense_variant	5/5		XP_011530993.1
SPMIP9	XM_011532692.3	c.150C>A	p.Asp50Glu	missense_variant	4/4		XP_011530994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX37	ENST00000303254.4	c.150C>A	p.Asp50Glu	missense_variant	4/4	1	NM_152670.3	ENSP00000307142.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2024

The c.150C>A (p.D50E) alteration is located in exon 4 (coding exon 3) of the TEX37 gene. This alteration results from a C to A substitution at nucleotide position 150, causing the aspartic acid (D) at amino acid position 50 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.13
DANN	Benign	0.86
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.058
Sift	Benign	0.14	T
Sift4G	Uncertain	0.054	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.078		Gain of helix (P = 0.0425);
MVP		0.10
MPC		0.069
ClinPred		0.033	T
GERP RS		-1.3
Varity_R		0.056
gMVP		0.015

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

LitVar

Other links and lift over

dbSNP: rs1673247124; hg19: chr2-88828599; COSMIC: COSV57556134;