NM_001388067.1:c.413A>G

Variant names:

• chr14-37270445-A-G
• rs147065074
• NM_001388067.1:c.413A>G

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.413A>G​(p.Asp138Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000554 in 1,444,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. D138N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MIPOL1 NM_001388067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38
• Publications: 1 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=0.16983002).

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.413A>G	p.Asp138Gly	missense	Exon 6 of 13	NP_001374996.1	Q8TD10-1
	MIPOL1	NM_001388069.1		c.413A>G	p.Asp138Gly	missense	Exon 6 of 13	NP_001374998.1	A0A8Q3SHY7
	MIPOL1	NM_001195296.2		c.413A>G	p.Asp138Gly	missense	Exon 8 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.413A>G	p.Asp138Gly	missense	Exon 6 of 13	ENSP00000506738.1	Q8TD10-1
	MIPOL1	ENST00000327441.11	TSL:1	c.413A>G	p.Asp138Gly	missense	Exon 7 of 14	ENSP00000333539.7	Q8TD10-1
	MIPOL1	ENST00000396294.7	TSL:1	c.413A>G	p.Asp138Gly	missense	Exon 8 of 15	ENSP00000379589.2	Q8TD10-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 240024 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000554 AC: 8 AN: 1444136 Hom.: 0 Cov.: 29 AF XY: 0.00000418 AC XY: 3 AN XY: 718458

African (AFR) AF: 0.00 AC: 0 AN: 32638

American (AMR) AF: 0.00 AC: 0 AN: 42472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25634

East Asian (EAS) AF: 0.00 AC: 0 AN: 38940

South Asian (SAS) AF: 0.00 AC: 0 AN: 83392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.00000544 AC: 6 AN: 1102948

Other (OTH) AF: 0.0000336 AC: 2 AN: 59518

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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	0.13
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.095
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.4
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.060
Sift	Benign	0.11	T
Sift4G	Benign	0.099	T
Polyphen		0.015	B
Vest4		0.32
MVP		0.62
MPC		0.036
ClinPred		0.76	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.27
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs147065074; hg19: chr14-37739650;