Variant rs12939757 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144775.3(SMCR8):c.*4276A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,252 control chromosomes in the GnomAD database, including 5,617 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 0.26 ( 5614 hom., cov: 33)

Exomes 𝑓: 0.32 ( 3 hom. )

Consequence

SMCR8
NM_144775.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.736

Variant links:

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]

SMCR8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMCR8	NM_144775.3 linkuse as main transcript	c.*4276A>G		3_prime_UTR_variant	2/2	ENST00000406438.5	NP_658988.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMCR8	ENST00000406438.5 linkuse as main transcript	c.*4276A>G		3_prime_UTR_variant	2/2	1	NM_144775.3	ENSP00000385025	P1	Q8TEV9-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39926

AN:

152062

Hom.:

5615

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.0735

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.319

AC:

AN:

Hom.:

Cov.:

AF XY:

0.278

AC XY:

AN XY:

show subpopulations

Gnomad4 AMR exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.750

Gnomad4 NFE exome

AF:

0.296

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.262

AC:

39936

AN:

152180

Hom.:

5614

Cov.:

AF XY:

0.259

AC XY:

19252

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.0741

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.312

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.294

Hom.:

6365

Bravo

AF:

0.249

Asia WGS

AF:

0.137

AC:

476

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.69

DANN

Benign

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over