17-18315490-T-C

Position:

• chr17-18315490-T-C

Variant summary

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

The NM_144775.3(SMCR8):​c.-300T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 333,798 control chromosomes in the GnomAD database, including 81,146 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 0.72 (40413 hom., cov: 34)
  • Exomes 𝑓: 0.66 (40733 hom.)
• Consequence: SMCR8 NM_144775.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581

Genes affected

SMCR8 (HGNC:17921): (SMCR8-C9orf72 complex subunit) Enables protein kinase binding activity and protein kinase inhibitor activity. Contributes to guanyl-nucleotide exchange factor activity. Involved in negative regulation of macromolecule metabolic process; regulation of TOR signaling; and regulation of macroautophagy. Located in chromatin; cytoplasm; and nucleoplasm. Part of guanyl-nucleotide exchange factor complex. Colocalizes with Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCR8	NM_144775.3	c.-300T>C		5_prime_UTR_variant	1/2	ENST00000406438.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCR8	ENST00000406438.5	c.-300T>C		5_prime_UTR_variant	1/2	1	NM_144775.3	P1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109828 AN: 152070 Hom.: 40362 Cov.: 34

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.709

GnomAD4 exome AF: 0.664 AC: 120503 AN: 181610 Hom.: 40733 Cov.: 1 AF XY: 0.660 AC XY: 61638 AN XY: 93426

Gnomad4 AFR exome AF: 0.854

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.722

Gnomad4 EAS exome AF: 0.519

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.670

Gnomad4 OTH exome AF: 0.681

GnomAD4 genome AF: 0.722 AC: 109945 AN: 152188 Hom.: 40413 Cov.: 34 AF XY: 0.719 AC XY: 53504 AN XY: 74400

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.707

Alfa AF: 0.687 Hom.: 6349

Bravo AF: 0.725

Asia WGS AF: 0.544 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1563634; hg19: chr17-18218804;