11-406529-A-T

Position:

• chr11-406529-A-T

Variant summary

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

The NM_001135054.2(SIGIRR):​c.889T>A​(p.Ser297Thr) 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: 33)
• Consequence: SIGIRR NM_001135054.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.31

Genes affected

SIGIRR (HGNC:30575): (single Ig and TIR domain containing) Predicted to enable NAD+ nucleosidase activity. Involved in negative regulation of DNA-binding transcription factor activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

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	Protein	UniProt
SIGIRR	NM_001135054.2	c.889T>A	p.Ser297Thr	missense_variant	9/10	ENST00000431843.7	NP_001128526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGIRR	ENST00000431843.7	c.889T>A	p.Ser297Thr	missense_variant	9/10	1	NM_001135054.2	ENSP00000403104.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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

May 05, 2023

The c.889T>A (p.S297T) alteration is located in exon 9 (coding exon 8) of the SIGIRR gene. This alteration results from a T to A substitution at nucleotide position 889, causing the serine (S) at amino acid position 297 to be replaced by a threonine (T). 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	Benign	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	.;.;T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M;M;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.020	D;D;D;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.98	D;D;D;D
Vest4		0.42
MutPred		0.51		Loss of phosphorylation at T294 (P = 0.1183);Loss of phosphorylation at T294 (P = 0.1183);Loss of phosphorylation at T294 (P = 0.1183);Loss of phosphorylation at T294 (P = 0.1183);
MVP		0.54
MPC		0.81
ClinPred		0.99	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.66
gMVP		0.27

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: chr11-406529;