14-37268773-C-A

Variant names:

• chr14-37268773-C-A
• rs779847251
• NM_001388067.1:c.367C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001388067.1(MIPOL1):​c.367C>A​(p.Leu123Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 1,584,682 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: MIPOL1 NM_001388067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13223886).

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.367C>A	p.Leu123Ile	missense	Exon 5 of 13	NP_001374996.1	Q8TD10-1
	MIPOL1	NM_001388069.1		c.367C>A	p.Leu123Ile	missense	Exon 5 of 13	NP_001374998.1	A0A8Q3SHY7
	MIPOL1	NM_001195296.2		c.367C>A	p.Leu123Ile	missense	Exon 7 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.367C>A	p.Leu123Ile	missense	Exon 5 of 13	ENSP00000506738.1	Q8TD10-1
	MIPOL1	ENST00000327441.11	TSL:1	c.367C>A	p.Leu123Ile	missense	Exon 6 of 14	ENSP00000333539.7	Q8TD10-1
	MIPOL1	ENST00000396294.7	TSL:1	c.367C>A	p.Leu123Ile	missense	Exon 7 of 15	ENSP00000379589.2	Q8TD10-1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000382 AC: 9 AN: 235600 AF XY: 0.0000470

Gnomad AFR exome AF: 0.000588

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: 0.00000698 AC: 10 AN: 1432616 Hom.: 0 Cov.: 26 AF XY: 0.00000421 AC XY: 3 AN XY: 713136

African (AFR) AF: 0.000218 AC: 7 AN: 32060

American (AMR) AF: 0.00 AC: 0 AN: 40594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38754

South Asian (SAS) AF: 0.00 AC: 0 AN: 82468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095016

Other (OTH) AF: 0.0000169 AC: 1 AN: 59224

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152066 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74268

African (AFR) AF: 0.000434 AC: 18 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.000147

ExAC AF: 0.0000330 AC: 4

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	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.047	D
Sift4G	Benign	0.25	T
Polyphen		0.99	D
Vest4		0.43
MVP		0.56
MPC		0.20
ClinPred		0.22	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.077
Mutation Taster		=92/8	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: rs779847251; hg19: chr14-37737978;