chr15-68946106-G-C

Variant names:

• chr15-68946106-G-C
• rs3743093
• NM_145658.4:c.572G>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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: 0.0000014 (0 hom.)
• Consequence: SPESP1 NM_145658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 0 publications found

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]

SPESP1-NOX5 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049667537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145658.4. 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
	SPESP1	NM_145658.4	MANE Select	c.572G>C	p.Gly191Ala	missense	Exon 2 of 2	NP_663633.1	Q6UW49
	SPESP1-NOX5	NM_001184780.2		c.29+15389G>C		intron	N/A	NP_001171709.1
	SPESP1-NOX5	NR_033671.3		n.193+15389G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPESP1	ENST00000310673.4	TSL:1 MANE Select	c.572G>C	p.Gly191Ala	missense	Exon 2 of 2	ENSP00000312284.3	Q6UW49
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.-109+15389G>C		intron	N/A	ENSP00000454143.1
	SPESP1-NOX5	ENST00000703585.1		c.29+15389G>C		intron	N/A	ENSP00000515387.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.15
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
Mutation Taster		=99/1	polymorphism

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: rs3743093; hg19: chr15-69238445;