1-152878462-A-C

Position:

• chr1-152878462-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030663.3(SMCP):​c.-21+16A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,540 control chromosomes in the GnomAD database, including 13,889 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (13885 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4 hom.)
• Consequence: SMCP NM_030663.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCP	NM_030663.3	c.-21+16A>C		intron_variant		ENST00000368765.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCP	ENST00000368765.4	c.-21+16A>C		intron_variant		1	NM_030663.3	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53953 AN: 151946 Hom.: 13838 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.145 AC: 69 AN: 476 Hom.: 4 Cov.: 0 AF XY: 0.143 AC XY: 42 AN XY: 294

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.356 AC: 54059 AN: 152064 Hom.: 13885 Cov.: 32 AF XY: 0.354 AC XY: 26289 AN XY: 74340

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.297

Alfa AF: 0.230 Hom.: 3111

Bravo AF: 0.383

Asia WGS AF: 0.451 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs3737861; hg19: chr1-152850938;