7-50107663-C-T

Variant names:

• chr7-50107663-C-T
• rs6972867
• NM_001161834.3:c.651+3252C>T

Variant summary

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

The NM_001161834.3(SPMIP7):​c.651+3252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,004 control chromosomes in the GnomAD database, including 46,076 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 0.78 (46076 hom., cov: 31)
• Consequence: SPMIP7 NM_001161834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPMIP7	NM_001161834.3	c.651+3252C>T		intron_variant	Intron 2 of 8	ENST00000297001.7	NP_001155306.3
SPMIP7	XM_011515052.2	c.651+3252C>T		intron_variant	Intron 2 of 7		XP_011513354.1
SPMIP7	XM_011515053.3	c.651+3252C>T		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.651+3252C>T		intron_variant	Intron 2 of 8	5	NM_001161834.3	ENSP00000297001.7
ZPBP	ENST00000450231.1	c.10+9590G>A		intron_variant	Intron 3 of 4	3		ENSP00000390054.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118127 AN: 151886 Hom.: 46050 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.778 AC: 118207 AN: 152004 Hom.: 46076 Cov.: 31 AF XY: 0.777 AC XY: 57744 AN XY: 74302

African (AFR) AF: 0.732 AC: 30333 AN: 41460

American (AMR) AF: 0.825 AC: 12599 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3470

East Asian (EAS) AF: 0.882 AC: 4552 AN: 5160

South Asian (SAS) AF: 0.726 AC: 3483 AN: 4798

European-Finnish (FIN) AF: 0.771 AC: 8118 AN: 10534

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54034 AN: 67984

Other (OTH) AF: 0.754 AC: 1592 AN: 2112

Alfa AF: 0.787 Hom.: 8232

Bravo AF: 0.781

Asia WGS AF: 0.740 AC: 2569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.72
PhyloP100		-1.5
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: rs6972867; hg19: chr7-50147259;