chr7-30157465-G-A

Position:

• chr7-30157465-G-A

Variant summary

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

The NM_152793.3(MTURN):​c.313G>A​(p.Asp105Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,450,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MTURN NM_152793.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.54

Genes affected

MTURN (HGNC:25457): (maturin, neural progenitor differentiation regulator homolog) Involved in negative regulation of NF-kappaB transcription factor activity; positive regulation of MAPK cascade; and positive regulation of megakaryocyte differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTURN	NM_152793.3	c.313G>A	p.Asp105Asn	missense_variant	3/3	ENST00000324453.13	NP_690006.2
MTURN	XM_005249652.4	c.313G>A	p.Asp105Asn	missense_variant	3/4		XP_005249709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTURN	ENST00000324453.13	c.313G>A	p.Asp105Asn	missense_variant	3/3	1	NM_152793.3	ENSP00000324204	P1
MTURN	ENST00000324489.5	c.214G>A	p.Asp72Asn	missense_variant	3/3	1		ENSP00000324755
MTURN	ENST00000409688.1	c.190G>A	p.Asp64Asn	missense_variant	2/2	2		ENSP00000386490

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1450726 Hom.: 0 Cov.: 30 AF XY: 0.00000554 AC XY: 4 AN XY: 721704

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

May 06, 2024

The c.313G>A (p.D105N) alteration is located in exon 3 (coding exon 3) of the MTURN gene. This alteration results from a G to A substitution at nucleotide position 313, causing the aspartic acid (D) at amino acid position 105 to be replaced by an asparagine (N). 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	0.25
BayesDel_addAF	Benign	-0.0050	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PROVEAN	Uncertain	-2.4	N;N;D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.59
MutPred		0.16		Loss of helix (P = 0.0626);.;.;
MVP		0.13
MPC		2.0
ClinPred		0.85	D
GERP RS		6.2
Varity_R		0.49
gMVP		0.41

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: chr7-30197081;