15-68946106-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145658.4(SPESP1):​c.572G>A​(p.Gly191Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,613,776 control chromosomes in the GnomAD database, including 276,493 homozygotes. 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: 𝑓 0.58 (25597 hom., cov: 32)
  • Exomes 𝑓: 0.58 (250896 hom.)
• Consequence: SPESP1 NM_145658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 30 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.6811095E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

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>A	p.Gly191Glu	missense	Exon 2 of 2	NP_663633.1	Q6UW49
	SPESP1-NOX5	NM_001184780.2		c.29+15389G>A		intron	N/A	NP_001171709.1
	SPESP1-NOX5	NR_033671.3		n.193+15389G>A		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>A	p.Gly191Glu	missense	Exon 2 of 2	ENSP00000312284.3	Q6UW49
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.-109+15389G>A		intron	N/A	ENSP00000454143.1
	SPESP1-NOX5	ENST00000703585.1		c.29+15389G>A		intron	N/A	ENSP00000515387.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87548 AN: 151888 Hom.: 25577 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.574

GnomAD2 exomes AF: 0.541 AC: 135921 AN: 251170 AF XY: 0.543

Gnomad AFR exome AF: 0.593

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.556

Gnomad EAS exome AF: 0.462

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.605

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.583 AC: 852027 AN: 1461770 Hom.: 250896 Cov.: 62 AF XY: 0.580 AC XY: 421430 AN XY: 727194

African (AFR) AF: 0.594 AC: 19892 AN: 33478

American (AMR) AF: 0.420 AC: 18771 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 14557 AN: 26134

East Asian (EAS) AF: 0.465 AC: 18458 AN: 39700

South Asian (SAS) AF: 0.441 AC: 38032 AN: 86250

European-Finnish (FIN) AF: 0.577 AC: 30839 AN: 53412

Middle Eastern (MID) AF: 0.505 AC: 2910 AN: 5768

European-Non Finnish (NFE) AF: 0.606 AC: 673856 AN: 1111912

Other (OTH) AF: 0.575 AC: 34712 AN: 60392

GnomAD4 genome AF: 0.576 AC: 87601 AN: 152006 Hom.: 25597 Cov.: 32 AF XY: 0.570 AC XY: 42352 AN XY: 74284

African (AFR) AF: 0.595 AC: 24668 AN: 41438

American (AMR) AF: 0.495 AC: 7558 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3472

East Asian (EAS) AF: 0.464 AC: 2395 AN: 5166

South Asian (SAS) AF: 0.441 AC: 2129 AN: 4824

European-Finnish (FIN) AF: 0.574 AC: 6065 AN: 10566

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40918 AN: 67954

Other (OTH) AF: 0.570 AC: 1201 AN: 2106

Alfa AF: 0.590 Hom.: 104285

Bravo AF: 0.573

TwinsUK AF: 0.597 AC: 2212

ALSPAC AF: 0.585 AC: 2255

ESP6500AA AF: 0.591 AC: 2602

ESP6500EA AF: 0.607 AC: 5216

ExAC AF: 0.549 AC: 66629

Asia WGS AF: 0.498 AC: 1734 AN: 3478

EpiCase AF: 0.608

EpiControl AF: 0.607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.39
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.000087	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.14	N
PhyloP100		0.15
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.049
ClinPred		0.0082	T
GERP RS		-0.35
Varity_R		0.064
gMVP		0.044
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: rs3743093; hg19: chr15-69238445; COSMIC: COSV52986310; COSMIC: COSV52986310;