rs7995033

Positions:

• chr13-25257750-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004685.5(MTMR6):​c.955A>G​(p.Ile319Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,610,606 control chromosomes in the GnomAD database, including 498,503 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.63 (34983 hom., cov: 34)
  • Exomes 𝑓: 0.79 (463520 hom.)
• Consequence: MTMR6 NM_004685.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

Genes affected

MTMR6 (HGNC:7453): (myotubularin related protein 6) Enables phosphatidylinositol-3,5-bisphosphate phosphatase activity and phosphatidylinositol-3-phosphatase activity. Involved in phosphatidylinositol dephosphorylation. Located in cytoplasm and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

MTMR6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.1354054E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR6	NM_004685.5	c.955A>G	p.Ile319Val	missense_variant	8/14	ENST00000381801.6	NP_004676.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR6	ENST00000381801.6	c.955A>G	p.Ile319Val	missense_variant	8/14	1	NM_004685.5	ENSP00000371221.5
MTMR6	ENST00000482345.2	c.1069A>G	p.Ile357Val	missense_variant	9/15	5		ENSP00000516657.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95320 AN: 152090 Hom.: 34994 Cov.: 34

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.681

GnomAD3 exomes AF: 0.698 AC: 174703 AN: 250364 Hom.: 65754 AF XY: 0.712 AC XY: 96374 AN XY: 135392

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.835

Gnomad EAS exome AF: 0.588

Gnomad SAS exome AF: 0.585

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.839

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.786 AC: 1146230 AN: 1458398 Hom.: 463520 Cov.: 35 AF XY: 0.783 AC XY: 568562 AN XY: 725750

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.485

Gnomad4 ASJ exome AF: 0.835

Gnomad4 EAS exome AF: 0.552

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.838

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.757

GnomAD4 genome AF: 0.626 AC: 95309 AN: 152208 Hom.: 34983 Cov.: 34 AF XY: 0.624 AC XY: 46417 AN XY: 74440

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.679

Alfa AF: 0.800 Hom.: 96589

Bravo AF: 0.588

TwinsUK AF: 0.827 AC: 3068

ALSPAC AF: 0.830 AC: 3199

ESP6500AA AF: 0.243 AC: 1072

ESP6500EA AF: 0.836 AC: 7189

ExAC AF: 0.698 AC: 84783

Asia WGS AF: 0.549 AC: 1910 AN: 3478

EpiCase AF: 0.827

EpiControl AF: 0.830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	7.1e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.27	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.23
Sift	Benign	0.61	T
Sift4G	Benign	0.83	T
Polyphen		0.0	B
Vest4		0.051
MPC		0.099
ClinPred		0.00063	T
GERP RS		3.0
Varity_R		0.037
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs7995033; hg19: chr13-25831888; COSMIC: COSV67807952; COSMIC: COSV67807952;