chr7-100615175-C-T

Variant names:

• chr7-100615175-C-T
• rs149991784
• NM_023948.5:c.700C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_023948.5(MOSPD3):​c.700C>T​(p.Arg234Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,974 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. R234Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: MOSPD3 NM_023948.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 1 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3632085).

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.700C>T	p.Arg234Trp	missense	Exon 5 of 5	NP_076438.1	O75425-1
	MOSPD3	NM_001040097.2		c.700C>T	p.Arg234Trp	missense	Exon 6 of 6	NP_001035186.1	O75425-1
	MOSPD3	NM_001040098.1		c.700C>T	p.Arg234Trp	missense	Exon 6 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.700C>T	p.Arg234Trp	missense	Exon 5 of 5	ENSP00000377522.2	O75425-1
	MOSPD3	ENST00000424091.2	TSL:1	c.670C>T	p.Arg224Trp	missense	Exon 5 of 5	ENSP00000404626.2	O75425-4
	MOSPD3	ENST00000921523.1		c.769C>T	p.Arg257Trp	missense	Exon 5 of 5	ENSP00000591582.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251332 AF XY: 0.0000663

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000458 AC: 67 AN: 1461774 Hom.: 0 Cov.: 35 AF XY: 0.0000481 AC XY: 35 AN XY: 727188

African (AFR) AF: 0.000597 AC: 20 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86250

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

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5690

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1112002

Other (OTH) AF: 0.000132 AC: 8 AN: 60384

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74432

African (AFR) AF: 0.000458 AC: 19 AN: 41522

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.000181

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

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	Uncertain	0.40
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.23
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.057	T
Polyphen		0.0020	B
Vest4		0.53
MVP		0.43
MPC		0.33
ClinPred		0.40	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.50
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149991784; hg19: chr7-100212798; COSMIC: COSV56158022; COSMIC: COSV56158022;