1-152884502-G-A

Variant names:

• chr1-152884502-G-A
• NM_030663.3:c.80G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030663.3(SMCP):​c.80G>A​(p.Cys27Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,676 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMCP NM_030663.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

Genes affected

SMCP (HGNC:6962): (sperm mitochondria associated cysteine rich protein) Sperm mitochondria differ in morphology and subcellular localization from those of somatic cells. They are elongated, flattened, and arranged circumferentially to form a helical coiled sheath in the midpiece of the sperm flagellum. The protein encoded by this gene localizes to the capsule associated with the mitochondrial outer membranes and is thought to function in the organization and stabilization of the helical structure of the sperm's mitochondrial sheath. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2693544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMCP	NM_030663.3	c.80G>A	p.Cys27Tyr	missense_variant	Exon 2 of 2	ENST00000368765.4	NP_109588.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCP	ENST00000368765.4	c.80G>A	p.Cys27Tyr	missense_variant	Exon 2 of 2	1	NM_030663.3	ENSP00000357754.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727126

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80G>A (p.C27Y) alteration is located in exon 2 (coding exon 1) of the SMCP gene. This alteration results from a G to A substitution at nucleotide position 80, causing the cysteine (C) at amino acid position 27 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.43
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Benign	0.11
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.27
MutPred		0.23		Loss of methylation at K30 (P = 0.1559);
MVP		0.58
MPC		0.052
ClinPred		0.98	D
GERP RS		2.5
Varity_R		0.61
gMVP		0.011

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: chr1-152856978;