8-17381144-G-T

Position:

• chr8-17381144-G-T

Variant summary

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

The NM_004686.5(MTMR7):​c.25-7904C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,054 control chromosomes in the GnomAD database, including 15,362 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15362 hom., cov: 32)
• Consequence: MTMR7 NM_004686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377

Genes affected

MTMR7 (HGNC:7454): (myotubularin related protein 7) This gene encodes a member of the myotubularin family of tyrosine/dual-specificity phosphatases. The encoded protein is characterized by four distinct domains that are conserved among all members of the myotubularin family: the glucosyltransferase, Rab-like GTPase activator and myotubularins domain, the Rac-induced recruitment domain, the protein tyrosine phosphatases and dual-specificity phosphatases domain and the suppressor of variegation 3-9, enhancer-of-zeste, and trithorax interaction domain. This protein dephosphorylates the target substrates phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. A pseudogene of this gene is found on chromosome 5. [provided by RefSeq, Mar 2009]

LOC102724838 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR7	NM_004686.5	c.25-7904C>A		intron_variant		ENST00000180173.10	NP_004677.3
MTMR7	XM_047422407.1	c.-324-7904C>A		intron_variant			XP_047278363.1
MTMR7	XM_047422408.1	c.25-7904C>A		intron_variant			XP_047278364.1
LOC102724838	XR_428318.4	n.554-324G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR7	ENST00000180173.10	c.25-7904C>A		intron_variant		1	NM_004686.5	ENSP00000180173.4
MTMR7	ENST00000521857.5	c.25-7904C>A		intron_variant		5		ENSP00000429733.1
MTMR7	ENST00000517317.5	n.25-7904C>A		intron_variant		5		ENSP00000431000.1
MTMR7	ENST00000521177.1	n.261-7904C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65687 AN: 151936 Hom.: 15355 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.432 AC: 65717 AN: 152054 Hom.: 15362 Cov.: 32 AF XY: 0.435 AC XY: 32301 AN XY: 74322

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.480

Alfa AF: 0.412 Hom.: 2881

Bravo AF: 0.435

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.78

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: rs7460082; hg19: chr8-17238653; COSMIC: COSV51670857;