7-50134227-G-A

Position:

• chr7-50134227-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.848G>A​(p.Gly283Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,391,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: SPATA48 NM_001161834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0370

Genes affected

SPATA48 (HGNC:):

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

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=0.046928942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA48	NM_001161834.3	c.848G>A	p.Gly283Glu	missense_variant	4/9	ENST00000297001.7
SPATA48	XM_011515052.2	c.848G>A	p.Gly283Glu	missense_variant	4/8
SPATA48	XM_011515053.3	c.848G>A	p.Gly283Glu	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPMIP7	ENST00000297001.7	c.848G>A	p.Gly283Glu	missense_variant	4/9	5	NM_001161834.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000689 AC: 1 AN: 145046 Hom.: 0 AF XY: 0.0000130 AC XY: 1 AN XY: 76850

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000174

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000216 AC: 30 AN: 1391320 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 17 AN XY: 685988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000251

Gnomad4 OTH exome AF: 0.0000347

GnomAD4 genome Cov.: 32

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

Jun 11, 2021

The c.848G>A (p.G283E) alteration is located in exon 4 (coding exon 4) of the C7orf72 gene. This alteration results from a G to A substitution at nucleotide position 848, causing the glycine (G) at amino acid position 283 to be replaced by a glutamic acid (E). 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	0.081
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.7
DANN	Benign	0.66
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.025
Sift	Benign	0.47	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.33		Loss of catalytic residue at K282 (P = 0.0392);
MVP		0.13
ClinPred		0.026	T
GERP RS		-1.6
Varity_R		0.045
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs1156814094; hg19: chr7-50173823;