rs3822735

Variant names:

• chr5-35799892-A-G
• rs3822735
• NM_024867.4:c.4831-76A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-35799892-A-G
• chr5-35799892-A-C
• chr5-35799892-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024867.4(SPEF2):​c.4831-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,508,870 control chromosomes in the GnomAD database, including 381,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38516 hom., cov: 31)
  • Exomes 𝑓: 0.71 (343192 hom.)
• Consequence: SPEF2 NM_024867.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0460
• Publications: 14 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):

• primary ciliary dyskinesia

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• spermatogenic failure 43

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000248969 (HGNC:59028):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 5-35799892-A-G is Benign according to our data. Variant chr5-35799892-A-G is described in ClinVar as Benign. ClinVar VariationId is 1244371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024867.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEF2	NM_024867.4	MANE Select	c.4831-76A>G		intron	N/A	NP_079143.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEF2	ENST00000356031.8	TSL:1 MANE Select	c.4831-76A>G		intron	N/A	ENSP00000348314.3	Q9C093-1
	SPEF2	ENST00000506526.5	TSL:1	n.*1995-76A>G		intron	N/A	ENSP00000426624.1	H0YAC0
	SPEF2	ENST00000440995.6	TSL:5	c.4816-76A>G		intron	N/A	ENSP00000412125.2	Q9C093-2

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107684 AN: 151846 Hom.: 38463 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.709 AC: 962556 AN: 1356906 Hom.: 343192 AF XY: 0.712 AC XY: 478955 AN XY: 673150

African (AFR) AF: 0.703 AC: 21890 AN: 31150

American (AMR) AF: 0.752 AC: 30317 AN: 40332

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 14801 AN: 22666

East Asian (EAS) AF: 0.843 AC: 32921 AN: 39046

South Asian (SAS) AF: 0.813 AC: 61702 AN: 75872

European-Finnish (FIN) AF: 0.723 AC: 36752 AN: 50826

Middle Eastern (MID) AF: 0.636 AC: 3459 AN: 5442

European-Non Finnish (NFE) AF: 0.696 AC: 720344 AN: 1035170

Other (OTH) AF: 0.716 AC: 40370 AN: 56402

GnomAD4 genome AF: 0.709 AC: 107796 AN: 151964 Hom.: 38516 Cov.: 31 AF XY: 0.713 AC XY: 52962 AN XY: 74270

African (AFR) AF: 0.700 AC: 28981 AN: 41414

American (AMR) AF: 0.700 AC: 10685 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2221 AN: 3466

East Asian (EAS) AF: 0.896 AC: 4640 AN: 5178

South Asian (SAS) AF: 0.826 AC: 3963 AN: 4796

European-Finnish (FIN) AF: 0.728 AC: 7683 AN: 10558

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47394 AN: 67972

Other (OTH) AF: 0.687 AC: 1448 AN: 2108

Alfa AF: 0.696 Hom.: 81179

Bravo AF: 0.705

Asia WGS AF: 0.829 AC: 2884 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.7
DANN	Benign	0.81
PhyloP100		-0.046
Mutation Taster		=100/0	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: rs3822735; hg19: chr5-35799994;