rs1286720532

Variant names:

• chr7-100613268-A-G
• rs1286720532
• NM_023948.5:c.280A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-100613268-A-G
• chr7-100613268-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_023948.5(MOSPD3):​c.280A>G​(p.Ile94Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000491 in 1,424,250 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: MOSPD3 NM_023948.5 missense, splice_region
• Scores: Splicing: ADA: 0.9755
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.280A>G	p.Ile94Val	missense splice_region	Exon 2 of 5	NP_076438.1	O75425-1
	MOSPD3	NM_001040097.2		c.280A>G	p.Ile94Val	missense splice_region	Exon 3 of 6	NP_001035186.1	O75425-1
	MOSPD3	NM_001040098.1		c.280A>G	p.Ile94Val	missense splice_region	Exon 3 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.280A>G	p.Ile94Val	missense splice_region	Exon 2 of 5	ENSP00000377522.2	O75425-1
	MOSPD3	ENST00000424091.2	TSL:1	c.280A>G	p.Ile94Val	missense splice_region	Exon 2 of 5	ENSP00000404626.2	O75425-4
	MOSPD3	ENST00000921523.1		c.280A>G	p.Ile94Val	missense splice_region	Exon 2 of 5	ENSP00000591582.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251396 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000491 AC: 7 AN: 1424250 Hom.: 0 Cov.: 31 AF XY: 0.00000423 AC XY: 3 AN XY: 709060

African (AFR) AF: 0.00 AC: 0 AN: 32536

American (AMR) AF: 0.000113 AC: 5 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25224

East Asian (EAS) AF: 0.00 AC: 0 AN: 38474

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083954

Other (OTH) AF: 0.0000171 AC: 1 AN: 58436

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.32
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.077	T
Polyphen		0.0	B
Vest4		0.48
MutPred		0.75		Gain of sheet (P = 0.1451)
MVP		0.69
MPC		0.26
ClinPred		0.58	D
GERP RS		3.8
Varity_R		0.17
gMVP		0.11
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.79
SpliceAI score (max)		0.14		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: rs1286720532; hg19: chr7-100210891;