chr1-152878462-A-C

Variant names:

• chr1-152878462-A-C
• rs3737861
• NM_030663.3:c.-21+16A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMCP	NM_030663.3	c.-21+16A>C		intron_variant	Intron 1 of 1	ENST00000368765.4	NP_109588.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCP	ENST00000368765.4	c.-21+16A>C		intron_variant	Intron 1 of 1	1	NM_030663.3	ENSP00000357754.3

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

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.138 AC: 59 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.105 AC: 4 AN: 38

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.714 AC: 29602 AN: 41484

American (AMR) AF: 0.292 AC: 4470 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3466

East Asian (EAS) AF: 0.566 AC: 2924 AN: 5166

South Asian (SAS) AF: 0.344 AC: 1662 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1387 AN: 10598

Middle Eastern (MID) AF: 0.269 AC: 78 AN: 290

European-Non Finnish (NFE) AF: 0.184 AC: 12506 AN: 67928

Other (OTH) AF: 0.297 AC: 627 AN: 2110

Alfa AF: 0.232 Hom.: 4229

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
PhyloP100		-0.32
PromoterAI		-0.00010	Neutral
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: rs3737861; hg19: chr1-152850938;