7-50141370-T-C

Position:

• chr7-50141370-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001161834.3(SPATA48):​c.1067T>C​(p.Leu356Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,278 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: 0.0000014 (0 hom.)
• Consequence: SPATA48 NM_001161834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.50

Genes affected

SPATA48 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13247272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA48	NM_001161834.3	c.1067T>C	p.Leu356Pro	missense_variant	7/9	ENST00000297001.7
SPATA48	XM_011515052.2	c.1025T>C	p.Leu342Pro	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPMIP7	ENST00000297001.7	c.1067T>C	p.Leu356Pro	missense_variant	7/9	5	NM_001161834.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397278 Hom.: 0 Cov.: 28 AF XY: 0.00000145 AC XY: 1 AN XY: 689304

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000560

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Oct 29, 2021

The c.1067T>C (p.L356P) alteration is located in exon 7 (coding exon 7) of the C7orf72 gene. This alteration results from a T to C substitution at nucleotide position 1067, causing the leucine (L) at amino acid position 356 to be replaced by a proline (P). 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	0.097
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	6.7
DANN	Benign	0.88
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Benign	0.22	T
Sift4G	Benign	0.24	T
Polyphen		0.73	P
Vest4		0.18
MutPred		0.39		Gain of glycosylation at L356 (P = 0.0078);
MVP		0.34
ClinPred		0.50	D
GERP RS		-1.9
Varity_R		0.16
gMVP		0.34

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: chr7-50180966;