chr1-156263540-C-A

Position:

• chr1-156263540-C-A

Variant summary

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

The NM_015327.3(SMG5):​c.1886G>T​(p.Ser629Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMG5 NM_015327.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14

Genes affected

SMG5 (HGNC:24644): (SMG5 nonsense mediated mRNA decay factor) SMG5 is involved in nonsense-mediated mRNA decay (Ohnishi et al., 2003 [PubMed 14636577]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMG5	NM_015327.3	c.1886G>T	p.Ser629Ile	missense_variant	13/22	ENST00000361813.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMG5	ENST00000361813.5	c.1886G>T	p.Ser629Ile	missense_variant	13/22	1	NM_015327.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2022

The c.1886G>T (p.S629I) alteration is located in exon 13 (coding exon 13) of the SMG5 gene. This alteration results from a G to T substitution at nucleotide position 1886, causing the serine (S) at amino acid position 629 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.95	P
Vest4		0.72
MutPred		0.22		Loss of phosphorylation at S629 (P = 9e-04);
MVP		0.59
MPC		0.90
ClinPred		0.93	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.50

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: chr1-156233331;