6-88064108-T-C

Position:

• chr6-88064108-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030960.3(SPACA1):​c.620T>C​(p.Met207Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPACA1 NM_030960.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

Genes affected

SPACA1 (HGNC:14967): (sperm acrosome associated 1) The correlation of anti-sperm antibodies with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as identification of proteins for targeted contraception, are dependent on the identification and characterization of relevant sperm antigens. The protein expressed by this gene is recognized by anti-sperm antibodies from infertile males. Furthermore, antibodies generated against the recombinant protein block in vitro fertilization. This protein localizes to the acrosomal membrane of spermatids and mature spermatozoa where it is thought to play a role in acrosomal morphogenesis and in sperm-egg binding and fusion, respectively. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09411132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPACA1	NM_030960.3	c.620T>C	p.Met207Thr	missense_variant	6/7	ENST00000237201.2
SPACA1	XM_011536160.3	c.374T>C	p.Met125Thr	missense_variant	6/7
SPACA1	XM_017011335.2	c.374T>C	p.Met125Thr	missense_variant	6/7
SPACA1	XM_047419385.1	c.639T>C	p.Asp213=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA1	ENST00000237201.2	c.620T>C	p.Met207Thr	missense_variant	6/7	1	NM_030960.3	P1
SPACA1	ENST00000462227.1	n.165T>C		non_coding_transcript_exon_variant	2/3	3
SPACA1	ENST00000462690.5	n.137-178T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

The c.620T>C (p.M207T) alteration is located in exon 6 (coding exon 6) of the SPACA1 gene. This alteration results from a T to C substitution at nucleotide position 620, causing the methionine (M) at amino acid position 207 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.96	N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.071
Sift	Benign	0.13	T
Sift4G	Benign	0.35	T
Polyphen		0.13	B
Vest4		0.25
MutPred		0.24		Gain of glycosylation at M207 (P = 0.0079);
MVP		0.18
MPC		0.43
ClinPred		0.46	T
GERP RS		4.5
Varity_R		0.19
gMVP		0.20

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: chr6-88773826;