rs3210908

Variant names:

• chr11-406483-T-A
• rs3210908
• NM_001135054.2:c.935A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-406483-T-A
• chr11-406483-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135054.2(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. 16/22 in silico tools predict 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: 38)
• Consequence: SIGIRR NM_001135054.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 52 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135054.2. 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
	SIGIRR	NM_001135054.2	MANE Select	c.935A>T	p.Gln312Leu	missense	Exon 9 of 10	NP_001128526.1
	SIGIRR	NM_001135053.2		c.935A>T	p.Gln312Leu	missense	Exon 9 of 10	NP_001128525.1
	SIGIRR	NM_021805.3		c.935A>T	p.Gln312Leu	missense	Exon 9 of 10	NP_068577.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGIRR	ENST00000431843.7	TSL:1 MANE Select	c.935A>T	p.Gln312Leu	missense	Exon 9 of 10	ENSP00000403104.2
	SIGIRR	ENST00000397632.7	TSL:1	c.935A>T	p.Gln312Leu	missense	Exon 9 of 10	ENSP00000380756.3
	SIGIRR	ENST00000714411.1		c.-56A>T		5_prime_UTR_premature_start_codon_gain	Exon 9 of 10	ENSP00000519681.1

Frequencies

GnomAD3 genomes Cov.: 38

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 38

Alfa AF: 0.00 Hom.: 110601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.016
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.028
Sift	Benign	0.27	T
Sift4G	Benign	0.34	T
Polyphen		0.012	B
Vest4		0.12
MutPred		0.39		Loss of disorder (P = 0.0358)
MVP		0.23
MPC		0.22
ClinPred		0.073	T
GERP RS		-2.8
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.29
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs3210908; hg19: chr11-406483;