chr7-100613630-G-C

Variant names:

• chr7-100613630-G-C
• rs754838660
• NM_023948.5:c.435G>C

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.435G>C​(p.Gln145His) 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. 13/21 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: 0.753
• 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=0.23595256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOSPD3	NM_023948.5	c.435G>C	p.Gln145His	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.435G>C	p.Gln145His	missense_variant	Exon 3 of 5	1	NM_023948.5	ENSP00000377522.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.435G>C (p.Q145H) alteration is located in exon 3 (coding exon 3) of the MOSPD3 gene. This alteration results from a G to C substitution at nucleotide position 435, causing the glutamine (Q) at amino acid position 145 to be replaced by a histidine (H). 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	0.13
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;T;T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.79	.;T;T;.;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.90	L;.;L;L;.
PhyloP100		0.75
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.84	N;N;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.079	T;T;T;T;T
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.99	D;.;D;D;.
Vest4		0.29
MutPred		0.15		Gain of catalytic residue at L144 (P = 0.1453);Gain of catalytic residue at L144 (P = 0.1453);Gain of catalytic residue at L144 (P = 0.1453);Gain of catalytic residue at L144 (P = 0.1453);.;
MVP		0.34
MPC		0.70
ClinPred		0.69	D
GERP RS		4.1
Varity_R		0.077
gMVP		0.47
Mutation Taster		=70/30	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: rs754838660; hg19: chr7-100211253;