5-35644519-T-G

Position:

• chr5-35644519-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024867.4(SPEF2):​c.579T>G​(p.Ile193Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPEF2 NM_024867.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02896005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPEF2	NM_024867.4	c.579T>G	p.Ile193Met	missense_variant	4/37	ENST00000356031.8	NP_079143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8	c.579T>G	p.Ile193Met	missense_variant	4/37	1	NM_024867.4	ENSP00000348314.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1440114 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 715768

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.042
DANN	Benign	0.42
DEOGEN2	Benign	0.011	.;.;T;T;.
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.58	T;T;T;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.029	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.;L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.68	N;N;.;N;N
REVEL	Benign	0.020
Sift	Benign	0.15	T;T;.;T;T
Sift4G	Benign	0.20	T;T;.;T;T
Polyphen		0.017	B;B;.;B;.
Vest4		0.087
MutPred		0.28		Loss of catalytic residue at L198 (P = 0.0522);Loss of catalytic residue at L198 (P = 0.0522);Loss of catalytic residue at L198 (P = 0.0522);Loss of catalytic residue at L198 (P = 0.0522);Loss of catalytic residue at L198 (P = 0.0522);
MVP		0.055
MPC		0.030
ClinPred		0.086	T
GERP RS		-9.6
Varity_R		0.062
gMVP		0.073

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs7706444; hg19: chr5-35644621;