Variant chr7-50104347-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001161834.3(SPATA48):c.587A>C(p.Gln196Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,541,752 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00090 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

SPATA48
NM_001161834.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.606

Variant links:

Genes affected

SPATA48 (HGNC:):

SPATA48 links:

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

SPMIP7 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0080216825).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPATA48	NM_001161834.3 linkuse as main transcript	c.587A>C	p.Gln196Pro	missense_variant	2/9	ENST00000297001.7	NP_001155306.3
SPATA48	XM_011515052.2 linkuse as main transcript	c.587A>C	p.Gln196Pro	missense_variant	2/8		XP_011513354.1
SPATA48	XM_011515053.3 linkuse as main transcript	c.587A>C	p.Gln196Pro	missense_variant	2/6		XP_011513355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPMIP7	ENST00000297001.7 linkuse as main transcript	c.587A>C	p.Gln196Pro	missense_variant	2/9	5	NM_001161834.3	ENSP00000297001	P1
ZPBP	ENST00000450231.1 linkuse as main transcript	c.10+12906T>G		intron_variant		3		ENSP00000390054

Frequencies

GnomAD3 genomes

AF:

0.000901

AC:

137

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00124

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000806

AC:

125

AN:

155002

Hom.:

AF XY:

0.000743

AC XY:

AN XY:

82124

show subpopulations

Gnomad AFR exome

AF:

0.000255

Gnomad AMR exome

AF:

0.00173

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:

0.00125

Gnomad OTH exome

AF:

0.00138

GnomAD4 exome

AF:

0.00114

AC:

1583

AN:

1389560

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

771

AN XY:

685198

show subpopulations

Gnomad4 AFR exome

AF:

0.000191

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000900

AC:

137

AN:

152192

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.00108

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000601

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

The c.587A>C (p.Q196P) alteration is located in exon 2 (coding exon 2) of the C7orf72 gene. This alteration results from a A to C substitution at nucleotide position 587, causing the glutamine (Q) at amino acid position 196 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

0.061

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.57

DANN

Benign

0.58

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.33

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.69

REVEL

Benign

0.0090

Sift

Benign

0.35

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.11

MVP

0.040

ClinPred

0.0024

GERP RS

-1.1

Varity_R

0.079

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over