8-17348068-T-G

Variant names:

• chr8-17348068-T-G
• rs4921542
• NM_004686.5:c.597+885A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004686.5(MTMR7):​c.597+885A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,096 control chromosomes in the GnomAD database, including 5,550 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 0.20 (5550 hom., cov: 31)
• Consequence: MTMR7 NM_004686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR7	NM_004686.5	c.597+885A>C		intron_variant	Intron 5 of 13	ENST00000180173.10	NP_004677.3
MTMR7	XM_047422407.1	c.249+885A>C		intron_variant	Intron 6 of 14		XP_047278363.1
MTMR7	XM_047422408.1	c.597+885A>C		intron_variant	Intron 5 of 10		XP_047278364.1
LOC102724838	XR_428318.4	n.201+2823T>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR7	ENST00000180173.10	c.597+885A>C		intron_variant	Intron 5 of 13	1	NM_004686.5	ENSP00000180173.4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30270 AN: 151978 Hom.: 5507 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.200 AC: 30364 AN: 152096 Hom.: 5550 Cov.: 31 AF XY: 0.209 AC XY: 15546 AN XY: 74340

African (AFR) AF: 0.394 AC: 16348 AN: 41448

American (AMR) AF: 0.247 AC: 3780 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3665 AN: 5162

South Asian (SAS) AF: 0.277 AC: 1332 AN: 4810

European-Finnish (FIN) AF: 0.147 AC: 1560 AN: 10588

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0437 AC: 2972 AN: 68020

Other (OTH) AF: 0.200 AC: 422 AN: 2112

Alfa AF: 0.105 Hom.: 7533

Bravo AF: 0.217

Asia WGS AF: 0.497 AC: 1726 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs4921542; hg19: chr8-17205577;