15-68946106-G-C

Variant names:

• chr15-68946106-G-C
• NM_145658.4:c.572G>C

Variant summary

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

The NM_145658.4(SPESP1):​c.572G>C​(p.Gly191Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G191E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPESP1 NM_145658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

Genes affected

SPESP1 (HGNC:15570): (sperm equatorial segment protein 1) The encoded protein is a human alloantigen involved in sperm-egg binding and fusion. [provided by RefSeq, Apr 2010]

NOX5 (HGNC:):

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=0.049667537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPESP1	NM_145658.4	c.572G>C	p.Gly191Ala	missense_variant	Exon 2 of 2	ENST00000310673.4	NP_663633.1
SPESP1-NOX5	NM_001184780.2	c.29+15389G>C		intron_variant	Intron 1 of 15		NP_001171709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPESP1	ENST00000310673.4	c.572G>C	p.Gly191Ala	missense_variant	Exon 2 of 2	1	NM_145658.4	ENSP00000312284.3
NOX5	ENST00000260364.9	c.-109+15389G>C		intron_variant	Intron 1 of 16	1		ENSP00000454143.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461866 Hom.: 0 Cov.: 62 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

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: 0.00000180

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	0.14
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.51
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.015
Sift	Benign	0.42	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.019
MutPred		0.17		Gain of sheet (P = 0.0477);
MVP		0.048
MPC		0.044
ClinPred		0.054	T
GERP RS		-0.35
Varity_R		0.036
gMVP		0.084

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-69238445;