NM_001039464.4:c.1988A>G

Variant names:

• chr1-54678793-A-G
• rs75269200
• NM_001039464.4:c.1988A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039464.4(MROH7):​c.1988A>G​(p.Lys663Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,080 control chromosomes in the GnomAD database, including 703 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (219 hom., cov: 32)
  • Exomes 𝑓: 0.011 (484 hom.)
• Consequence: MROH7 NM_001039464.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 9 publications found

Genes affected

MROH7 (HGNC:24802): (maestro heat like repeat family member 7) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

MROH7-TTC4 (HGNC:49180): (MROH7-TTC4 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MROH7 (maestro heat-like repeat family member 7) and TTC4 (tetratricopeptide repeat domain 4) genes. Alternative splicing results in multiple transcript variants, which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to produce protein products. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025929213).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH7	NM_001039464.4	c.1988A>G	p.Lys663Arg	missense_variant	Exon 11 of 24	ENST00000421030.7	NP_001034553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH7	ENST00000421030.7	c.1988A>G	p.Lys663Arg	missense_variant	Exon 11 of 24	2	NM_001039464.4	ENSP00000396622.2
MROH7-TTC4	ENST00000414150.6	n.1988A>G		non_coding_transcript_exon_variant	Exon 11 of 33	2		ENSP00000410192.2

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5262 AN: 152138 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.0233 AC: 5823 AN: 249570 AF XY: 0.0227

Gnomad AFR exome AF: 0.0883

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0184

Gnomad EAS exome AF: 0.0693

Gnomad FIN exome AF: 0.0388

Gnomad NFE exome AF: 0.00282

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0105 AC: 15414 AN: 1461824 Hom.: 484 Cov.: 31 AF XY: 0.0112 AC XY: 8142 AN XY: 727216

African (AFR) AF: 0.0908 AC: 3040 AN: 33472

American (AMR) AF: 0.0108 AC: 485 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 445 AN: 26134

East Asian (EAS) AF: 0.0821 AC: 3257 AN: 39690

South Asian (SAS) AF: 0.0440 AC: 3797 AN: 86248

European-Finnish (FIN) AF: 0.0369 AC: 1970 AN: 53414

Middle Eastern (MID) AF: 0.0120 AC: 69 AN: 5766

European-Non Finnish (NFE) AF: 0.00123 AC: 1365 AN: 1111994

Other (OTH) AF: 0.0163 AC: 986 AN: 60386

GnomAD4 genome AF: 0.0348 AC: 5293 AN: 152256 Hom.: 219 Cov.: 32 AF XY: 0.0369 AC XY: 2747 AN XY: 74458

African (AFR) AF: 0.0898 AC: 3730 AN: 41522

American (AMR) AF: 0.0153 AC: 234 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.0665 AC: 344 AN: 5172

South Asian (SAS) AF: 0.0578 AC: 279 AN: 4828

European-Finnish (FIN) AF: 0.0397 AC: 421 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00251 AC: 171 AN: 68030

Other (OTH) AF: 0.0260 AC: 55 AN: 2112

Alfa AF: 0.0127 Hom.: 283

Bravo AF: 0.0339

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0767 AC: 302

ESP6500EA AF: 0.00290 AC: 24

ExAC AF: 0.0250 AC: 3019

Asia WGS AF: 0.0870 AC: 300 AN: 3478

EpiCase AF: 0.00169

EpiControl AF: 0.00196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0042	.;T;.;.
Eigen	Benign	-0.0099
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.60	T;T;T;T
MetaRNN	Benign	0.0026	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.3	.;L;.;L
PhyloP100		2.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.87	N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.93	P;B;.;.
Vest4		0.14
MPC		0.29
ClinPred		0.025	T
GERP RS		3.9
Varity_R		0.074
gMVP		0.12
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75269200; hg19: chr1-55144466; COSMIC: COSV59868097;