chr5-35644519-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024867.4(SPEF2):ā€‹c.579T>Cā€‹(p.Ile193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,591,038 control chromosomes in the GnomAD database, including 356,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.70 ( 37557 hom., cov: 32)
Exomes š‘“: 0.66 ( 318968 hom. )

Consequence

SPEF2
NM_024867.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.13
Variant links:
Genes affected
SPEF2 (HGNC:26293): (sperm flagellar 2) Involved in sperm axoneme assembly. Located in sperm flagellum. Implicated in spermatogenic failure 43. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
Variant 5-35644519-T-C is Benign according to our data. Variant chr5-35644519-T-C is described in ClinVar as [Benign]. Clinvar id is 403472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.13 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPEF2NM_024867.4 linkuse as main transcriptc.579T>C p.Ile193= synonymous_variant 4/37 ENST00000356031.8 NP_079143.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPEF2ENST00000356031.8 linkuse as main transcriptc.579T>C p.Ile193= synonymous_variant 4/371 NM_024867.4 ENSP00000348314 P2Q9C093-1

Frequencies

GnomAD3 genomes
AF:
0.698
AC:
106056
AN:
151918
Hom.:
37496
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.774
Gnomad AMI
AF:
0.509
Gnomad AMR
AF:
0.725
Gnomad ASJ
AF:
0.660
Gnomad EAS
AF:
0.869
Gnomad SAS
AF:
0.826
Gnomad FIN
AF:
0.609
Gnomad MID
AF:
0.627
Gnomad NFE
AF:
0.643
Gnomad OTH
AF:
0.674
GnomAD3 exomes
AF:
0.707
AC:
162203
AN:
229368
Hom.:
58134
AF XY:
0.703
AC XY:
87402
AN XY:
124254
show subpopulations
Gnomad AFR exome
AF:
0.779
Gnomad AMR exome
AF:
0.794
Gnomad ASJ exome
AF:
0.663
Gnomad EAS exome
AF:
0.866
Gnomad SAS exome
AF:
0.815
Gnomad FIN exome
AF:
0.628
Gnomad NFE exome
AF:
0.641
Gnomad OTH exome
AF:
0.680
GnomAD4 exome
AF:
0.663
AC:
953405
AN:
1439002
Hom.:
318968
Cov.:
33
AF XY:
0.666
AC XY:
476156
AN XY:
715286
show subpopulations
Gnomad4 AFR exome
AF:
0.779
Gnomad4 AMR exome
AF:
0.781
Gnomad4 ASJ exome
AF:
0.659
Gnomad4 EAS exome
AF:
0.875
Gnomad4 SAS exome
AF:
0.810
Gnomad4 FIN exome
AF:
0.633
Gnomad4 NFE exome
AF:
0.637
Gnomad4 OTH exome
AF:
0.678
GnomAD4 genome
AF:
0.698
AC:
106183
AN:
152036
Hom.:
37557
Cov.:
32
AF XY:
0.699
AC XY:
51961
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.775
Gnomad4 AMR
AF:
0.725
Gnomad4 ASJ
AF:
0.660
Gnomad4 EAS
AF:
0.868
Gnomad4 SAS
AF:
0.826
Gnomad4 FIN
AF:
0.609
Gnomad4 NFE
AF:
0.643
Gnomad4 OTH
AF:
0.677
Alfa
AF:
0.652
Hom.:
52204
Bravo
AF:
0.707
Asia WGS
AF:
0.830
AC:
2886
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Spermatogenic failure 43 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 15, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.36
DANN
Benign
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

LitVar

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

Other links and lift over

dbSNP: rs7706444; hg19: chr5-35644621; API