Genetic Variant SMCR8:c.*697C>T (chr17-18323767-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000406438.5(SMCR8):c.*697C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 153,336 control chromosomes in the GnomAD database, including 13,309 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 0.39 ( 13232 hom., cov: 34)

Exomes 𝑓: 0.35 ( 77 hom. )

Consequence

SMCR8
ENST00000406438.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.36

Publications

18 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000406438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCR8	NM_144775.3	MANE Select	c.*697C>T		3_prime_UTR	Exon 2 of 2	NP_658988.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCR8	ENST00000406438.5	TSL:1 MANE Select	c.*697C>T		3_prime_UTR	Exon 2 of 2	ENSP00000385025.3

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

59025

AN:

152112

Hom.:

13195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.0777

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.365

GnomAD4 exome

AF:

0.352

AC:

389

AN:

1106

Hom.:

Cov.:

AF XY:

0.339

AC XY:

200

AN XY:

590

show subpopulations

African (AFR)

AF:

0.583

AC:

AN:

American (AMR)

AF:

0.357

AC:

AN:

140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.231

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.358

AC:

305

AN:

852

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.388

AC:

59121

AN:

152230

Hom.:

13232

Cov.:

AF XY:

0.381

AC XY:

28378

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.614

AC:

25522

AN:

41534

American (AMR)

AF:

0.290

AC:

4435

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

1241

AN:

3472

East Asian (EAS)

AF:

0.0783

AC:

406

AN:

5188

South Asian (SAS)

AF:

0.198

AC:

956

AN:

4824

European-Finnish (FIN)

AF:

0.325

AC:

3444

AN:

10604

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21944

AN:

67988

Other (OTH)

AF:

0.366

AC:

773

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1783

3566

5348

7131

8914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.338

Hom.:

28731

Bravo

AF:

0.393

Asia WGS

AF:

0.192

AC:

669

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.9

(source)

DANN

Benign

0.63

PhyloP100

-2.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over