chr7-100613527-G-A

Variant names:

• chr7-100613527-G-A
• rs200656454
• NM_023948.5:c.332G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_023948.5(MOSPD3):​c.332G>A​(p.Arg111His) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R111S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: MOSPD3 NM_023948.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10604665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOSPD3	NM_023948.5	c.332G>A	p.Arg111His	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.332G>A	p.Arg111His	missense_variant	Exon 3 of 5	1	NM_023948.5	ENSP00000377522.2

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251456 AF XY: 0.0000809

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000924

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26 AN XY: 727248

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: 26136

East Asian (EAS) AF: 0.000957 AC: 38 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1112012

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000111 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000824 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332G>A (p.R111H) alteration is located in exon 3 (coding exon 3) of the MOSPD3 gene. This alteration results from a G to A substitution at nucleotide position 332, causing the arginine (R) at amino acid position 111 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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.71	D;.;D;D;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.71	.;T;T;.;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.55	N;.;N;N;.
PhyloP100		4.2
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D
REVEL	Uncertain	0.41
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		1.0	D;.;D;D;.
Vest4		0.77
MVP		0.86
MPC		0.45
ClinPred		0.25	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.50
Mutation Taster		=89/11	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: rs200656454; hg19: chr7-100211150; COSMIC: COSV56158332;