chr14-37268704-C-T

Variant names:

• chr14-37268704-C-T
• rs142664639
• NM_001388067.1:c.298C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001388067.1(MIPOL1):​c.298C>T​(p.Pro100Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P100A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MIPOL1 NM_001388067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06728926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIPOL1	NM_001388067.1	c.298C>T	p.Pro100Ser	missense_variant	Exon 5 of 13	ENST00000684589.1	NP_001374996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIPOL1	ENST00000684589.1	c.298C>T	p.Pro100Ser	missense_variant	Exon 5 of 13		NM_001388067.1	ENSP00000506738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450092 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 721714

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: 0.00

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.8
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	.;T;T;T;T;T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.72	T;.;.;T;.;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.067	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L;L;.;.;.;.;L
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.5	D;N;N;N;N;D;N;N
REVEL	Benign	0.043
Sift	Pathogenic	0.0	D;T;T;T;T;T;T;T
Sift4G	Pathogenic	0.0	D;T;T;T;T;T;T;T
Polyphen		0.052, 0.10	.;B;B;.;B;.;B;B
Vest4		0.21, 0.22, 0.21, 0.23
MutPred		0.33		Loss of catalytic residue at P100 (P = 0.0197);Loss of catalytic residue at P100 (P = 0.0197);Loss of catalytic residue at P100 (P = 0.0197);.;.;Loss of catalytic residue at P100 (P = 0.0197);.;Loss of catalytic residue at P100 (P = 0.0197);
MVP		0.21
MPC		0.031
ClinPred		0.20	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.089

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142664639; hg19: chr14-37737909;