5-35803475-C-T

Variant names:

• chr5-35803475-C-T
• rs931555
• NM_024867.4:c.5011-3232C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024867.4(SPEF2):​c.5011-3232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,106 control chromosomes in the GnomAD database, including 5,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5388 hom., cov: 32)
• Consequence: SPEF2 NM_024867.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.891
• Publications: 24 publications found

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]

SPEF2 Gene-Disease associations (from GenCC):

• spermatogenic failure 43

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000248969 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEF2	NM_024867.4	c.5011-3232C>T		intron_variant	Intron 34 of 36	ENST00000356031.8	NP_079143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8	c.5011-3232C>T		intron_variant	Intron 34 of 36	1	NM_024867.4	ENSP00000348314.3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36326 AN: 151988 Hom.: 5392 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36324 AN: 152106 Hom.: 5388 Cov.: 32 AF XY: 0.241 AC XY: 17894 AN XY: 74354

African (AFR) AF: 0.0728 AC: 3022 AN: 41506

American (AMR) AF: 0.196 AC: 2998 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3466

East Asian (EAS) AF: 0.209 AC: 1081 AN: 5170

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4816

European-Finnish (FIN) AF: 0.405 AC: 4287 AN: 10578

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22181 AN: 67958

Other (OTH) AF: 0.216 AC: 455 AN: 2108

Alfa AF: 0.287 Hom.: 22751

Bravo AF: 0.216

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.63
DANN	Benign	0.56
PhyloP100		-0.89
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs931555; hg19: chr5-35803577;