rs774355338

Variant names:

• chr5-179821121-G-A
• NM_003900.5:c.185G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-179821121-G-A
• chr5-179821121-G-C
• chr5-179821121-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003900.5(SQSTM1):​c.185G>A​(p.Gly62Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000818 in 1,222,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: SQSTM1 NM_003900.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23911753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SQSTM1	NM_003900.5	c.185G>A	p.Gly62Asp	missense_variant	Exon 1 of 8	ENST00000389805.9	NP_003891.1
SQSTM1	NM_001142298.2	c.-47-1837G>A		intron_variant	Intron 2 of 8		NP_001135770.1
SQSTM1	NM_001142299.2	c.-47-1837G>A		intron_variant	Intron 2 of 8		NP_001135771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SQSTM1	ENST00000389805.9	c.185G>A	p.Gly62Asp	missense_variant	Exon 1 of 8	1	NM_003900.5	ENSP00000374455.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.18e-7 AC: 1 AN: 1222918 Hom.: 0 Cov.: 31 AF XY: 0.00000168 AC XY: 1 AN XY: 593636

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.73	T;.;T;.
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.66	N;.;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.8	N;.;N;N
REVEL	Benign	0.17
Sift	Benign	0.13	T;.;T;T
Sift4G	Benign	0.69	T;D;T;T
Polyphen		0.11	B;.;.;D
Vest4		0.53
MutPred		0.43		Loss of catalytic residue at G62 (P = 0.0242);Loss of catalytic residue at G62 (P = 0.0242);Loss of catalytic residue at G62 (P = 0.0242);Loss of catalytic residue at G62 (P = 0.0242);
MVP		0.82
MPC		0.42
ClinPred		0.56	D
GERP RS		2.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
Varity_R		0.31
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-179248121;