chr22-23834542-T-G

Position:

• chr22-23834542-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003073.5(SMARCB1):​c.*362T>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 0.00095 in 660,216 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (1 hom.)
• Consequence: SMARCB1 NM_003073.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0150

Genes affected

SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

DERL3 (HGNC:14236): (derlin 3) The protein encoded by this gene belongs to the derlin family, and resides in the endoplasmic reticulum (ER). Proteins that are unfolded or misfolded in the ER must be refolded or degraded to maintain the homeostasis of the ER. This protein appears to be involved in the degradation of misfolded glycoproteins in the ER. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

DERL3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-23834542-T-G is Benign according to our data. Variant chr22-23834542-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1204849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00307 (402/130872) while in subpopulation AFR AF= 0.0151 (347/23014). AF 95% confidence interval is 0.0138. There are 4 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 402 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCB1	NM_003073.5	c.*362T>G		3_prime_UTR_variant	9/9	ENST00000644036.2	NP_003064.2
DERL3	NM_001002862.3	c.*2327A>C		3_prime_UTR_variant	7/7	ENST00000318109.12	NP_001002862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2	c.*362T>G		3_prime_UTR_variant	9/9		NM_003073.5	ENSP00000494049.2
DERL3	ENST00000318109	c.*2327A>C		3_prime_UTR_variant	7/7	1	NM_001002862.3	ENSP00000315303.8

Frequencies

GnomAD3 genomes AF: 0.00307 AC: 402 AN: 130822 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00312

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.0000896

Gnomad OTH AF: 0.00221

GnomAD4 exome AF: 0.000425 AC: 225 AN: 529344 Hom.: 1 Cov.: 4 AF XY: 0.000344 AC XY: 99 AN XY: 287780

Gnomad4 AFR exome AF: 0.0168

Gnomad4 AMR exome AF: 0.000646

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000326

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000578

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.00307 AC: 402 AN: 130872 Hom.: 4 Cov.: 31 AF XY: 0.00311 AC XY: 200 AN XY: 64362

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.00311

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000896

Gnomad4 OTH AF: 0.00218

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00295

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 02, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116375770; hg19: chr22-24176729;