7-50120593-A-G

Variant names:

• chr7-50120593-A-G
• rs1379175
• NM_001161834.3:c.652-9124A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161834.3(SPMIP7):​c.652-9124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,068 control chromosomes in the GnomAD database, including 53,257 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53257 hom., cov: 31)
• Consequence: SPMIP7 NM_001161834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 4 publications found

Genes affected

SPMIP7 (HGNC:22564): (sperm microtubule inner protein 7)

ZPBP (HGNC:15662): (zona pellucida binding protein) ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998 [PubMed 9378618]).[supplied by OMIM, Aug 2008]

ZPBP Gene-Disease associations (from GenCC):

• spermatogenic failure 66

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPMIP7	NM_001161834.3	c.652-9124A>G		intron_variant	Intron 2 of 8	ENST00000297001.7	NP_001155306.3
SPMIP7	XM_011515052.2	c.652-9124A>G		intron_variant	Intron 2 of 7		XP_011513354.1
SPMIP7	XM_011515053.3	c.652-9124A>G		intron_variant	Intron 2 of 5		XP_011513355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPMIP7	ENST00000297001.7	c.652-9124A>G		intron_variant	Intron 2 of 8	5	NM_001161834.3	ENSP00000297001.7
ZPBP	ENST00000450231.1	c.-346-197T>C		intron_variant	Intron 1 of 4	3		ENSP00000390054.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127106 AN: 151950 Hom.: 53200 Cov.: 31

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.815

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.837 AC: 127222 AN: 152068 Hom.: 53257 Cov.: 31 AF XY: 0.835 AC XY: 62033 AN XY: 74322

African (AFR) AF: 0.833 AC: 34543 AN: 41478

American (AMR) AF: 0.859 AC: 13115 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2672 AN: 3470

East Asian (EAS) AF: 0.923 AC: 4777 AN: 5176

South Asian (SAS) AF: 0.800 AC: 3846 AN: 4810

European-Finnish (FIN) AF: 0.796 AC: 8410 AN: 10566

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57079 AN: 67982

Other (OTH) AF: 0.816 AC: 1725 AN: 2114

Alfa AF: 0.836 Hom.: 73275

Bravo AF: 0.841

Asia WGS AF: 0.865 AC: 3006 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.50
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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: rs1379175; hg19: chr7-50160189;