7-100612856-G-T

Variant names:

• chr7-100612856-G-T
• rs775947023
• NM_023948.5:c.65G>T

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.65G>T​(p.Arg22Leu) 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. 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. R22Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOSPD3 NM_023948.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• 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=0.25042698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOSPD3	NM_023948.5	c.65G>T	p.Arg22Leu	missense_variant	Exon 1 of 5	ENST00000393950.7	NP_076438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOSPD3	ENST00000393950.7	c.65G>T	p.Arg22Leu	missense_variant	Exon 1 of 5	1	NM_023948.5	ENSP00000377522.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;T;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.85	.;T;T;.;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;.;N;N;N
PhyloP100		1.5
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.69	N;N;N;N;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.99	D;.;D;D;.
Vest4		0.51
MutPred		0.33		Loss of solvent accessibility (P = 3e-04);Loss of solvent accessibility (P = 3e-04);Loss of solvent accessibility (P = 3e-04);Loss of solvent accessibility (P = 3e-04);Loss of solvent accessibility (P = 3e-04);
MVP		0.38
MPC		1.2
ClinPred		0.74	D
GERP RS		4.2
PromoterAI		-0.015	Neutral
Varity_R		0.21
gMVP		0.32
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs775947023; hg19: chr7-100210479; COSMIC: COSV56158849; COSMIC: COSV56158849;