chr7-100613526-C-G

Variant names:

• chr7-100613526-C-G
• rs200292497
• NM_023948.5:c.331C>G

Variant summary

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

The NM_023948.5(MOSPD3):​c.331C>G​(p.Arg111Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R111H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MOSPD3 NM_023948.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOSPD3	NM_023948.5	c.331C>G	p.Arg111Gly	missense_variant	Exon 3 of 5	ENST00000393950.7	NP_076438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOSPD3	ENST00000393950.7	c.331C>G	p.Arg111Gly	missense_variant	Exon 3 of 5	1	NM_023948.5	ENSP00000377522.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.84	D;.;D;D;.
Eigen	Benign	-0.0011
Eigen_PC	Benign	0.026
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.73	.;T;T;.;T
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.55	N;.;N;N;.
PhyloP100		1.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.99	D;.;D;D;.
Vest4		0.85
MutPred		0.66		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);.;
MVP		0.84
MPC		1.1
ClinPred		0.88	D
GERP RS		2.2
Varity_R		0.63
gMVP		0.67
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200292497; hg19: chr7-100211149;