rs12676388

Positions:

• chr8-17372243-C-A

Variant summary

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

The NM_004686.5(MTMR7):​c.147+875G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,102 control chromosomes in the GnomAD database, including 1,794 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 0.14 (1794 hom., cov: 31)
• Consequence: MTMR7 NM_004686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR7	NM_004686.5	c.147+875G>T		intron_variant		ENST00000180173.10	NP_004677.3
LOC102724838	XR_428318.4	n.202-7574C>A		intron_variant, non_coding_transcript_variant
MTMR7	XM_047422407.1	c.-202+875G>T		intron_variant			XP_047278363.1
MTMR7	XM_047422408.1	c.147+875G>T		intron_variant			XP_047278364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR7	ENST00000180173.10	c.147+875G>T		intron_variant		1	NM_004686.5	ENSP00000180173	P1
MTMR7	ENST00000521857.5	c.147+875G>T		intron_variant		5		ENSP00000429733
MTMR7	ENST00000517317.5	c.147+875G>T		intron_variant, NMD_transcript_variant		5		ENSP00000431000

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20896 AN: 151984 Hom.: 1782 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.138 AC: 20945 AN: 152102 Hom.: 1794 Cov.: 31 AF XY: 0.140 AC XY: 10412 AN XY: 74352

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0642

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.130

Alfa AF: 0.140 Hom.: 919

Bravo AF: 0.129

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.28

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: rs12676388; hg19: chr8-17229752;