7-100612831-C-G

Variant names:

• chr7-100612831-C-G
• rs1802867450
• NM_023948.5:c.40C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023948.5(MOSPD3):​c.40C>G​(p.Pro14Ala) 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: MOSPD3 NM_023948.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.490
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09608549).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023948.5. 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
	MOSPD3	NM_023948.5	MANE Select	c.40C>G	p.Pro14Ala	missense	Exon 1 of 5	NP_076438.1	O75425-1
	MOSPD3	NM_001040097.2		c.40C>G	p.Pro14Ala	missense	Exon 2 of 6	NP_001035186.1	O75425-1
	MOSPD3	NM_001040098.1		c.40C>G	p.Pro14Ala	missense	Exon 2 of 6	NP_001035187.1	O75425-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOSPD3	ENST00000393950.7	TSL:1 MANE Select	c.40C>G	p.Pro14Ala	missense	Exon 1 of 5	ENSP00000377522.2	O75425-1
	MOSPD3	ENST00000424091.2	TSL:1	c.40C>G	p.Pro14Ala	missense	Exon 1 of 5	ENSP00000404626.2	O75425-4
	MOSPD3	ENST00000921523.1		c.40C>G	p.Pro14Ala	missense	Exon 1 of 5	ENSP00000591582.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.3
DANN	Benign	0.97
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.49
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.11
Sift	Benign	0.081	T
Sift4G	Benign	0.093	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.11		Loss of glycosylation at P14 (P = 0.0546)
MVP		0.20
MPC		0.30
ClinPred		0.084	T
GERP RS		1.2
PromoterAI		0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.042
gMVP		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1802867450; hg19: chr7-100210454;