rs12560201

chrX-64332496-A-G

Variant summary

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

The NM_017677.4(MTMR8):c.1152-739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 111,763 control chromosomes in the GnomAD database, including 207 homozygotes. There are 1,833 hemizygotes in GnomAD. 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 0.060 (207 hom., 1833 hem., cov: 23)
• Consequence: MTMR8 NM_017677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

Genes affected

MTMR8 (HGNC:16825): (myotubularin related protein 8) This gene encodes a member of the myotubularin-related family and is part of the MTMR6 subgroup. Family members are dual-specificity phosphatases and the encoded protein contains a phosphoinositide-binding domain (PID) and a SET-interacting domain (SID). Defects in other family members have been found in myotubular myopathic diseases. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR8	NM_017677.4	c.1152-739T>C		intron_variant		ENST00000374852.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR8	ENST00000374852.4	c.1152-739T>C		intron_variant		1	NM_017677.4	P1
MTMR8	ENST00000462447.5	n.312-739T>C		intron_variant, non_coding_transcript_variant		3
MTMR8	ENST00000478487.5	n.351-739T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 6699 AN: 111711 Hom.: 207 Cov.: 23 AF XY: 0.0541 AC XY: 1834 AN XY: 33883

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.0642

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000845

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0797

Gnomad MID AF: 0.0213

Gnomad NFE AF: 0.0978

Gnomad OTH AF: 0.0444

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

GnomAD4 genome AF: 0.0599 AC: 6696 AN: 111763 Hom.: 207 Cov.: 23 AF XY: 0.0540 AC XY: 1833 AN XY: 33945

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.000848

Gnomad4 SAS AF: 0.0140

Gnomad4 FIN AF: 0.0797

Gnomad4 NFE AF: 0.0978

Gnomad4 OTH AF: 0.0438

Alfa AF: 0.0808 Hom.: 1625

Bravo AF: 0.0544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.8
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12560201; hg19: chrX-63552376;