chr11-406483-T-A

Position:

• chr11-406483-T-A

Variant summary

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

The ENST00000431843.7(SIGIRR):​c.935A>T​(p.Gln312Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q312R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 38)
• Consequence: SIGIRR ENST00000431843.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06950873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGIRR	NM_001135054.2	c.935A>T	p.Gln312Leu	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.935A>T	p.Gln312Leu	missense_variant	9/10	1	NM_001135054.2	ENSP00000403104	P1

Frequencies

GnomAD3 genomes Cov.: 38

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.18
DANN	Benign	0.56
DEOGEN2	Benign	0.051	T;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.34	.;.;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.070	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L;L;L;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.028
Sift	Benign	0.27	T;T;T;T
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.012	B;B;B;B
Vest4		0.12
MutPred		0.39		Loss of disorder (P = 0.0358);Loss of disorder (P = 0.0358);Loss of disorder (P = 0.0358);Loss of disorder (P = 0.0358);
MVP		0.23
MPC		0.22
ClinPred		0.073	T
GERP RS		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3210908; hg19: chr11-406483;