Variant 17-18316293-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_144775.3(SMCR8):c.504G>A(p.Gln168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,614,016 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

SMCR8
NM_144775.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.719

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 17-18316293-G-A is Benign according to our data. Variant chr17-18316293-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647556.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.719 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMCR8	NM_144775.3 linkuse as main transcript	c.504G>A	p.Gln168=	synonymous_variant	1/2	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.504G>A	p.Gln168=	synonymous_variant	1/2	1	NM_144775.3	ENSP00000385025	P1	Q8TEV9-1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00265

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00152

AC:

382

AN:

251022

Hom.:

AF XY:

0.00150

AC XY:

204

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000745

Gnomad NFE exome

AF:

0.00275

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00228

AC:

3330

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

1570

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000976

Gnomad4 NFE exome

AF:

0.00280

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00142

AC:

216

AN:

152246

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00265

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00159

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

SMCR8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.0

DANN

Benign

0.84

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over