NM_001100878.2:c.1975G>T

Variant names:

• chr8-143567424-C-A
• rs573154588
• NM_001100878.2:c.1975G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100878.2(MROH6):​c.1975G>T​(p.Ala659Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000854 in 1,170,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A659T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045514762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.1975G>T	p.Ala659Ser	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.1975G>T	p.Ala659Ser	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 8.54e-7 AC: 1 AN: 1170796 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 562710

African (AFR) AF: 0.00 AC: 0 AN: 23918

American (AMR) AF: 0.00 AC: 0 AN: 11066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15926

East Asian (EAS) AF: 0.00 AC: 0 AN: 27546

South Asian (SAS) AF: 0.00 AC: 0 AN: 44550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 967462

Other (OTH) AF: 0.0000210 AC: 1 AN: 47540

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.0
DANN	Benign	0.64
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.41
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.0080
Sift	Benign	0.78	T
Sift4G	Benign	0.089	T
Polyphen		0.022	B
Vest4		0.10
MutPred		0.26		Gain of glycosylation at A659 (P = 0.0113);
MVP		0.014
MPC		0.020
ClinPred		0.040	T
GERP RS		-0.57
Varity_R		0.035
gMVP		0.056
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs573154588; hg19: chr8-144649594;