14-37268682-T-A

Position:

• chr14-37268682-T-A

Variant summary

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

The NM_001388067.1(MIPOL1):​c.276T>A​(p.Asp92Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIPOL1 NM_001388067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.220

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]

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=0.10365257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIPOL1	NM_001388067.1	c.276T>A	p.Asp92Glu	missense_variant	5/13	ENST00000684589.1	NP_001374996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIPOL1	ENST00000684589.1	c.276T>A	p.Asp92Glu	missense_variant	5/13		NM_001388067.1	ENSP00000506738	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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 14, 2024

The c.276T>A (p.D92E) alteration is located in exon 7 (coding exon 3) of the MIPOL1 gene. This alteration results from a T to A substitution at nucleotide position 276, causing the aspartic acid (D) at amino acid position 92 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	.;T;T;T;T;T;T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.57	T;.;.;T;.;T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.10	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L;L;.;.;.;.;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.6	D;N;N;N;N;D;N;N
REVEL	Benign	0.067
Sift	Pathogenic	0.0	D;D;D;D;T;D;T;D
Sift4G	Pathogenic	0.0	D;T;T;T;T;D;T;T
Polyphen		0.89, 0.79	.;P;P;.;P;.;P;P
Vest4		0.091, 0.093, 0.11
MutPred		0.24		Gain of disorder (P = 0.0907);Gain of disorder (P = 0.0907);Gain of disorder (P = 0.0907);.;.;Gain of disorder (P = 0.0907);.;Gain of disorder (P = 0.0907);
MVP		0.52
MPC		0.029
ClinPred		0.92	D
GERP RS		2.7
Varity_R		0.060
gMVP		0.036

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr14-37737887;