rs771973965

Variant names:

• chr15-68946055-T-C
• rs771973965
• NM_145658.4:c.521T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-68946055-T-C
• chr15-68946055-T-G

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.521T>C​(p.Val174Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,070 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SPESP1 NM_145658.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.633
• Publications: 1 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=0.03785011).

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.521T>C	p.Val174Ala	missense	Exon 2 of 2	NP_663633.1	Q6UW49
	SPESP1-NOX5	NM_001184780.2		c.29+15338T>C		intron	N/A	NP_001171709.1
	SPESP1-NOX5	NR_033671.3		n.193+15338T>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.521T>C	p.Val174Ala	missense	Exon 2 of 2	ENSP00000312284.3	Q6UW49
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.-109+15338T>C		intron	N/A	ENSP00000454143.1
	SPESP1-NOX5	ENST00000703585.1		c.29+15338T>C		intron	N/A	ENSP00000515387.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251282 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14 AN XY: 727242

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: 39698

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000306 AC: 34 AN: 1112002

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

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.41
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.63
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.019
Sift	Benign	0.41	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.056
MVP		0.030
MPC		0.047
ClinPred		0.055	T
GERP RS		-6.4
Varity_R		0.032
gMVP		0.059
Mutation Taster		=100/0	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: rs771973965; hg19: chr15-69238394;