chr7-50096135-G-A

Position:

• chr7-50096135-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001161834.3(SPATA48):​c.50G>A​(p.Arg17Lys) 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. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA48 NM_001161834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.139

Genes affected

SPATA48 (HGNC:):

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04163012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA48	NM_001161834.3	c.50G>A	p.Arg17Lys	missense_variant	1/9	ENST00000297001.7	NP_001155306.3
SPATA48	XM_011515052.2	c.50G>A	p.Arg17Lys	missense_variant	1/8		XP_011513354.1
SPATA48	XM_011515053.3	c.50G>A	p.Arg17Lys	missense_variant	1/6		XP_011513355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPMIP7	ENST00000297001.7	c.50G>A	p.Arg17Lys	missense_variant	1/9	5	NM_001161834.3	ENSP00000297001	P1
ZPBP	ENST00000450231.1	c.11-6426C>T		intron_variant		3		ENSP00000390054

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.50G>A (p.R17K) alteration is located in exon 1 (coding exon 1) of the C7orf72 gene. This alteration results from a G to A substitution at nucleotide position 50, causing the arginine (R) at amino acid position 17 to be replaced by a lysine (K). 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	0.082
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.2
DANN	Benign	0.95
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.023
Sift	Benign	0.59	T
Sift4G	Benign	0.92	T
Polyphen		0.0010	B
Vest4		0.029
MutPred		0.30		Gain of ubiquitination at R17 (P = 0.0258);
MVP		0.055
ClinPred		0.041	T
GERP RS		2.4
Varity_R		0.042
gMVP		0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-50135731;