NM_001142298.2:c.-156-313C>T

Variant names:

• chr5-179811261-C-T
• rs72807343
• NM_001142298.2:c.-156-313C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001142298.2(SQSTM1):​c.-156-313C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 151,424 control chromosomes in the GnomAD database, including 39 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 0.016 (39 hom., cov: 26)
• Consequence: SQSTM1 NM_001142298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 12 publications found

Genes affected

SQSTM1 (HGNC:11280): (sequestosome 1) This gene encodes a multifunctional protein that binds ubiquitin and regulates activation of the nuclear factor kappa-B (NF-kB) signaling pathway. The protein functions as a scaffolding/adaptor protein in concert with TNF receptor-associated factor 6 to mediate activation of NF-kB in response to upstream signals. Alternatively spliced transcript variants encoding either the same or different isoforms have been identified for this gene. Mutations in this gene result in sporadic and familial Paget disease of bone. [provided by RefSeq, Mar 2009]

SQSTM1 Gene-Disease associations (from GenCC):

• neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• frontotemporal dementia and/or amyotrophic lateral sclerosis 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
• osteosarcoma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• Paget disease of bone 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• behavioral variant of frontotemporal dementia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• frontotemporal dementia with motor neuron disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000301422 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0164 (2476/151424) while in subpopulation AFR AF = 0.0217 (895/41244). AF 95% confidence interval is 0.0205. There are 39 homozygotes in GnomAd4. There are 1137 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142298.2. 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
	SQSTM1	NM_001142298.2		c.-156-313C>T		intron	N/A	NP_001135770.1
	SQSTM1	NM_001142299.2		c.-156-313C>T		intron	N/A	NP_001135771.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SQSTM1	ENST00000514093.5	TSL:5	c.-156-313C>T		intron	N/A	ENSP00000427308.1
	SQSTM1	ENST00000506042.5	TSL:2	n.195-313C>T		intron	N/A
	SQSTM1	ENST00000506690.1	TSL:2	n.1105-313C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2476 AN: 151322 Hom.: 38 Cov.: 26

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.00391

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0164 AC: 2476 AN: 151424 Hom.: 39 Cov.: 26 AF XY: 0.0154 AC XY: 1137 AN XY: 74002

African (AFR) AF: 0.0217 AC: 895 AN: 41244

American (AMR) AF: 0.0146 AC: 221 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3462

East Asian (EAS) AF: 0.00214 AC: 11 AN: 5144

South Asian (SAS) AF: 0.0163 AC: 78 AN: 4776

European-Finnish (FIN) AF: 0.00391 AC: 41 AN: 10492

Middle Eastern (MID) AF: 0.0172 AC: 5 AN: 290

European-Non Finnish (NFE) AF: 0.0153 AC: 1039 AN: 67824

Other (OTH) AF: 0.0162 AC: 34 AN: 2100

Alfa AF: 0.0152 Hom.: 3

Bravo AF: 0.0170

Asia WGS AF: 0.0130 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.3
DANN	Benign	0.79
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs72807343; hg19: chr5-179238261;