7-100612804-G-A

Position:

• chr7-100612804-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023948.5(MOSPD3):​c.13G>A​(p.Ala5Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOSPD3 NM_023948.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

Genes affected

MOSPD3 (HGNC:25078): (motile sperm domain containing 3) This gene encodes a multi-pass membrane protein with a major sperm protein (MSP) domain. The deletion of a similar mouse gene is associated with defective cardiac development and neonatal lethality. Alternate transcriptional splice variants, encoding different isoforms, have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23779482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOSPD3	NM_023948.5	c.13G>A	p.Ala5Thr	missense_variant	1/5	ENST00000393950.7	NP_076438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOSPD3	ENST00000393950.7	c.13G>A	p.Ala5Thr	missense_variant	1/5	1	NM_023948.5	ENSP00000377522.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 21, 2023

The c.13G>A (p.A5T) alteration is located in exon 1 (coding exon 1) of the MOSPD3 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the alanine (A) at amino acid position 5 to be replaced by a threonine (T). 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	0.21
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.072	T;.;T;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.82	.;T;T;.;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.0	N;.;N;N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.43	N;N;N;N;N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.037	D;D;D;D;D
Polyphen		0.99	D;.;D;D;.
Vest4		0.42
MutPred		0.17		Gain of phosphorylation at A5 (P = 0.0016);Gain of phosphorylation at A5 (P = 0.0016);Gain of phosphorylation at A5 (P = 0.0016);Gain of phosphorylation at A5 (P = 0.0016);Gain of phosphorylation at A5 (P = 0.0016);
MVP		0.40
MPC		1.0
ClinPred		0.77	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr7-100210427;