chr8-143567282-C-A

Variant names:

• chr8-143567282-C-A
• NM_001100878.2:c.2117G>T

Variant summary

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

The NM_001100878.2(MROH6):​c.2117G>T​(p.Ser706Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000934 in 1,070,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

Genes affected

MROH6 (HGNC:27814): (maestro heat like repeat family member 6)

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=0.18737552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2117G>T	p.Ser706Ile	missense_variant	Exon 14 of 14	ENST00000398882.8	NP_001094348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH6	ENST00000398882.8	c.2117G>T	p.Ser706Ile	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.34e-7 AC: 1 AN: 1070926 Hom.: 0 Cov.: 30 AF XY: 0.00000198 AC XY: 1 AN XY: 505618

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000123

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

May 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2117G>T (p.S706I) alteration is located in exon 14 (coding exon 14) of the MROH6 gene. This alteration results from a G to T substitution at nucleotide position 2117, causing the serine (S) at amino acid position 706 to be replaced by an isoleucine (I). 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	0.26
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.017	T;.;.;.
Eigen	Benign	0.017
Eigen_PC	Benign	-0.092
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.46	.;.;.;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.25
MutPred		0.17		Loss of phosphorylation at S706 (P = 0.0242);.;.;.;
MVP		0.15
MPC		0.062
ClinPred		0.84	D
GERP RS		5.0
Varity_R		0.30
gMVP		0.34

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: chr8-144649452;