chr14-37369563-A-G

Position:

• chr14-37369563-A-G

Variant summary

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

The NM_001388067.1(MIPOL1):​c.875A>G​(p.Gln292Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MIPOL1 NM_001388067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73

Genes affected

MIPOL1 (HGNC:21460): (mirror-image polydactyly 1) This gene encodes a coiled-coil domain-containing protein. The encoded protein may function as a tumor suppressor. A translocation that results in truncation of the protein encoded by this locus has been associated with mirror-image polydactyly, also known as Laurin-Sandrow Syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2010]

MIPOL1 (HGNC:):

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
MIPOL1	NM_001388067.1	c.875A>G	p.Gln292Arg	missense_variant	10/13	ENST00000684589.1	NP_001374996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIPOL1	ENST00000684589.1	c.875A>G	p.Gln292Arg	missense_variant	10/13		NM_001388067.1	ENSP00000506738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461306 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726982

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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

Dec 13, 2022

The c.875A>G (p.Q292R) alteration is located in exon 12 (coding exon 8) of the MIPOL1 gene. This alteration results from a A to G substitution at nucleotide position 875, causing the glutamine (Q) at amino acid position 292 to be replaced by an arginine (R). 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	0.16
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T;T;T;T;T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.77	.;.;T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.59	D;D;D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.81	L;L;.;.;.;L
MutationTaster	Benign	0.87	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.015	D;D;D;D;D;D
Sift4G	Benign	0.24	T;T;T;T;T;T
Polyphen		1.0	D;D;.;D;D;D
Vest4		0.75
MutPred		0.10		Gain of MoRF binding (P = 0.0067);Gain of MoRF binding (P = 0.0067);.;.;.;Gain of MoRF binding (P = 0.0067);
MVP		0.64
MPC		0.22
ClinPred		0.85	D
GERP RS		5.2
Varity_R		0.15
gMVP		0.25

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: chr14-37838768;