2-88529181-C-T

Position:

• chr2-88529181-C-T

Variant summary

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

The NM_152670.3(SPMIP9):​c.250C>T​(p.Pro84Ser) 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 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPMIP9 NM_152670.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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 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/exons	MANE	Protein	UniProt
SPMIP9	NM_152670.3	c.250C>T	p.Pro84Ser	missense_variant	4/4	ENST00000303254.4	NP_689883.1
SPMIP9	XM_005264188.4	c.250C>T	p.Pro84Ser	missense_variant	4/4		XP_005264245.3
SPMIP9	XM_011532691.2	c.250C>T	p.Pro84Ser	missense_variant	5/5		XP_011530993.1
SPMIP9	XM_011532692.3	c.250C>T	p.Pro84Ser	missense_variant	4/4		XP_011530994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX37	ENST00000303254.4	c.250C>T	p.Pro84Ser	missense_variant	4/4	1	NM_152670.3	ENSP00000307142.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Dec 19, 2023

The c.250C>T (p.P84S) alteration is located in exon 4 (coding exon 3) of the TEX37 gene. This alteration results from a C to T substitution at nucleotide position 250, causing the proline (P) at amino acid position 84 to be replaced by a serine (S). 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	0.26
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.30		Gain of glycosylation at P84 (P = 0.0225);
MVP		0.48
MPC		0.42
ClinPred		0.98	D
GERP RS		2.8
Varity_R		0.71
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr2-88828699; COSMIC: COSV105144913;