2-88529167-A-G

Position:

• chr2-88529167-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000303254.4(SPMIP9):​c.236A>G​(p.Lys79Arg) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPMIP9 ENST00000303254.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

Genes affected

TEX37 (HGNC:):

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030457288).
• BP6: Variant 2-88529167-A-G is Benign according to our data. Variant chr2-88529167-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3322284.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX37	NM_152670.3	c.236A>G	p.Lys79Arg	missense_variant	4/4	ENST00000303254.4	NP_689883.1
TEX37	XM_005264188.4	c.236A>G	p.Lys79Arg	missense_variant	4/4		XP_005264245.3
TEX37	XM_011532691.2	c.236A>G	p.Lys79Arg	missense_variant	5/5		XP_011530993.1
TEX37	XM_011532692.3	c.236A>G	p.Lys79Arg	missense_variant	4/4		XP_011530994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPMIP9	ENST00000303254.4	c.236A>G	p.Lys79Arg	missense_variant	4/4	1	NM_152670.3	ENSP00000307142	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.15
DANN	Benign	0.65
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.77	N
REVEL	Benign	0.038
Sift	Benign	0.71	T
Sift4G	Benign	0.92	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.13		Loss of ubiquitination at K79 (P = 0.0183);
MVP		0.055
MPC		0.060
ClinPred		0.053	T
GERP RS		-8.7
Varity_R		0.020
gMVP		0.032

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: chr2-88828685;