rs78576797

Variant names:

• chr5-35695742-T-C
• rs78576797
• NM_024867.4:c.1983T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-35695742-T-C
• chr5-35695742-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024867.4(SPEF2):​c.1983T>C​(p.Asn661Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,609,400 control chromosomes in the GnomAD database, including 706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (69 hom., cov: 32)
  • Exomes 𝑓: 0.023 (637 hom.)
• Consequence: SPEF2 NM_024867.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.860
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-35695742-T-C is Benign according to our data. Variant chr5-35695742-T-C is described in ClinVar as Benign. ClinVar VariationId is 403476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.86 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEF2	NM_024867.4	c.1983T>C	p.Asn661Asn	synonymous_variant	Exon 14 of 37	ENST00000356031.8	NP_079143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8	c.1983T>C	p.Asn661Asn	synonymous_variant	Exon 14 of 37	1	NM_024867.4	ENSP00000348314.3

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3309 AN: 152206 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0762

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0271 AC: 6586 AN: 243186 AF XY: 0.0297

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0849

Gnomad EAS exome AF: 0.00496

Gnomad FIN exome AF: 0.0323

Gnomad NFE exome AF: 0.0221

Gnomad OTH exome AF: 0.0347

GnomAD4 exome AF: 0.0228 AC: 33235 AN: 1457076 Hom.: 637 Cov.: 29 AF XY: 0.0245 AC XY: 17744 AN XY: 724486

African (AFR) AF: 0.0132 AC: 440 AN: 33312

American (AMR) AF: 0.0130 AC: 576 AN: 44246

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 2202 AN: 25970

East Asian (EAS) AF: 0.00296 AC: 117 AN: 39574

South Asian (SAS) AF: 0.0611 AC: 5206 AN: 85142

European-Finnish (FIN) AF: 0.0322 AC: 1716 AN: 53238

Middle Eastern (MID) AF: 0.0882 AC: 507 AN: 5746

European-Non Finnish (NFE) AF: 0.0187 AC: 20730 AN: 1109686

Other (OTH) AF: 0.0289 AC: 1741 AN: 60162

GnomAD4 genome AF: 0.0218 AC: 3319 AN: 152324 Hom.: 69 Cov.: 32 AF XY: 0.0230 AC XY: 1712 AN XY: 74486

African (AFR) AF: 0.0141 AC: 586 AN: 41584

American (AMR) AF: 0.0181 AC: 277 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0762 AC: 264 AN: 3466

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5188

South Asian (SAS) AF: 0.0549 AC: 265 AN: 4830

European-Finnish (FIN) AF: 0.0312 AC: 331 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0220 AC: 1494 AN: 68026

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0230 Hom.: 46

Bravo AF: 0.0201

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant 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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.57
PhyloP100		-0.86
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: rs78576797; hg19: chr5-35695844;