rs267606563

Variant names:

• chr11-67490170-A-C
• rs267606563
• NM_003977.4:c.601A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-67490170-A-C
• chr11-67490170-A-T

Variant summary

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

The NM_003977.4(AIP):​c.601A>C​(p.Lys201Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K201R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AIP NM_003977.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07
• Publications: 0 publications found

Genes affected

AIP (HGNC:358): (aryl hydrocarbon receptor interacting protein) The protein encoded by this gene is a receptor for aryl hydrocarbons and a ligand-activated transcription factor. The encoded protein is found in the cytoplasm as part of a multiprotein complex, but upon binding of ligand is transported to the nucleus. This protein can regulate the expression of many xenobiotic metabolizing enzymes. Also, the encoded protein can bind specifically to and inhibit the activity of hepatitis B virus. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

MIR6752 (HGNC:50020): (microRNA 6752) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	NM_003977.4	MANE Select	c.601A>C	p.Lys201Gln	missense	Exon 4 of 6	NP_003968.3
	AIP	NM_001302960.2		c.601A>C	p.Lys201Gln	missense	Exon 4 of 6	NP_001289889.1
	AIP	NM_001302959.2		c.424A>C	p.Lys142Gln	missense	Exon 4 of 6	NP_001289888.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	ENST00000279146.8	TSL:1 MANE Select	c.601A>C	p.Lys201Gln	missense	Exon 4 of 6	ENSP00000279146.3
	AIP	ENST00000934218.1		c.691A>C	p.Lys231Gln	missense	Exon 4 of 6	ENSP00000604277.1
	AIP	ENST00000872352.1		c.601A>C	p.Lys201Gln	missense	Exon 4 of 6	ENSP00000542411.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.12	T
PhyloP100		7.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.010	D
Sift4G	Benign	0.088	T
Vest4		0.69
MutPred		0.49		Loss of ubiquitination at K201 (P = 0.0255)
MVP		0.73
MPC		1.2
ClinPred		0.95	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.69
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs267606563; hg19: chr11-67257641;