chr14-37266979-A-C

Variant names:

• chr14-37266979-A-C
• NM_001388067.1:c.61A>C

Variant summary

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

The NM_001388067.1(MIPOL1):​c.61A>C​(p.Asn21His) 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. 13/22 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: 1.09
• Publications: 0 publications found

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

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=0.094564706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388067.1. 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
	MIPOL1	NM_001388067.1	MANE Select	c.61A>C	p.Asn21His	missense	Exon 4 of 13	NP_001374996.1	Q8TD10-1
	MIPOL1	NM_001388069.1		c.61A>C	p.Asn21His	missense	Exon 4 of 13	NP_001374998.1	A0A8Q3SHY7
	MIPOL1	NM_001195296.2		c.61A>C	p.Asn21His	missense	Exon 6 of 15	NP_001182225.1	Q8TD10-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIPOL1	ENST00000684589.1	MANE Select	c.61A>C	p.Asn21His	missense	Exon 4 of 13	ENSP00000506738.1	Q8TD10-1
	MIPOL1	ENST00000327441.11	TSL:1	c.61A>C	p.Asn21His	missense	Exon 5 of 14	ENSP00000333539.7	Q8TD10-1
	MIPOL1	ENST00000396294.7	TSL:1	c.61A>C	p.Asn21His	missense	Exon 6 of 15	ENSP00000379589.2	Q8TD10-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.090
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.067	T
Polyphen		0.037	B
Vest4		0.16
MutPred		0.061		Loss of helix (P = 0.0376)
MVP		0.43
MPC		0.031
ClinPred		0.17	T
GERP RS		2.8
Varity_R		0.066
gMVP		0.082
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr14-37736184;