15-30941871-T-C

Position:

• chr15-30941871-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017762.3(MTMR10):​c.1933A>G​(p.Ile645Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTMR10 NM_017762.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.111

Genes affected

MTMR10 (HGNC:25999): (myotubularin related protein 10) Predicted to enable phosphatidylinositol-3-phosphatase activity. Predicted to be involved in phosphatidylinositol dephosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAN1 (HGNC:29170): (FANCD2 and FANCI associated nuclease 1) This gene plays a role in DNA interstrand cross-link repair and encodes a protein with 5' flap endonuclease and 5'-3' exonuclease activity. Mutations in this gene cause karyomegalic interstitial nephritis. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2016]

MTMR10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14420289).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR10	NM_017762.3	c.1933A>G	p.Ile645Val	missense_variant	16/16	ENST00000435680.6	NP_060232.2
FAN1	NM_014967.5	c.*309T>C		3_prime_UTR_variant	15/15	ENST00000362065.9	NP_055782.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR10	ENST00000435680.6	c.1933A>G	p.Ile645Val	missense_variant	16/16	1	NM_017762.3	ENSP00000402537.1
FAN1	ENST00000362065.9	c.*309T>C		3_prime_UTR_variant	15/15	1	NM_014967.5	ENSP00000354497.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.1933A>G (p.I645V) alteration is located in exon 16 (coding exon 16) of the MTMR10 gene. This alteration results from a A to G substitution at nucleotide position 1933, causing the isoleucine (I) at amino acid position 645 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.9
DANN	Benign	0.97
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.087
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.050	T
Polyphen		0.099	B
Vest4		0.081
MutPred		0.43		Gain of glycosylation at S650 (P = 0.136);
MVP		0.59
MPC		0.17
ClinPred		0.13	T
GERP RS		-1.1
Varity_R		0.074
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-31234074;