NM_001039464.4:c.191C>G

Variant names:

• chr1-54653117-C-G
• rs150191046
• NM_001039464.4:c.191C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001039464.4(MROH7):​c.191C>G​(p.Ser64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,614,186 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: MROH7 NM_001039464.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.225
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004191786).
• BP6: Variant 1-54653117-C-G is Benign according to our data. Variant chr1-54653117-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2638830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039464.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH7	NM_001039464.4	MANE Select	c.191C>G	p.Ser64Cys	missense	Exon 3 of 24	NP_001034553.3	Q68CQ1-7
	MROH7	NM_001291332.2		c.-214+11149C>G		intron	N/A	NP_001278261.1
	MROH7	NR_026782.3		n.477C>G		non_coding_transcript_exon	Exon 3 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH7	ENST00000421030.7	TSL:2 MANE Select	c.191C>G	p.Ser64Cys	missense	Exon 3 of 24	ENSP00000396622.2	Q68CQ1-7
	MROH7-TTC4	ENST00000414150.6	TSL:2	n.191C>G		non_coding_transcript_exon	Exon 3 of 33	ENSP00000410192.2	A0A0A0MT08
	MROH7	ENST00000422659.5	TSL:1	n.191C>G		non_coding_transcript_exon	Exon 2 of 23	ENSP00000388181.1	Q68CQ1-8

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 381 AN: 152182 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00813

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000662 AC: 165 AN: 249270 AF XY: 0.000555

Gnomad AFR exome AF: 0.00814

Gnomad AMR exome AF: 0.000696

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.0000885

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000298 AC: 436 AN: 1461886 Hom.: 1 Cov.: 46 AF XY: 0.000298 AC XY: 217 AN XY: 727244

African (AFR) AF: 0.00818 AC: 274 AN: 33480

American (AMR) AF: 0.000648 AC: 29 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1112008

Other (OTH) AF: 0.000960 AC: 58 AN: 60396

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152300 Hom.: 7 Cov.: 32 AF XY: 0.00231 AC XY: 172 AN XY: 74466

African (AFR) AF: 0.00828 AC: 344 AN: 41568

American (AMR) AF: 0.00170 AC: 26 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68036

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.000508 Hom.: 0

Bravo AF: 0.00288

ESP6500AA AF: 0.00836 AC: 32

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000885 AC: 107

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.0
DANN	Benign	0.95
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.23
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.062
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Polyphen		0.79	P
Vest4		0.22
MVP		0.030
MPC		0.18
ClinPred		0.0097	T
GERP RS		2.7
Varity_R		0.10
gMVP		0.11
Mutation Taster		=94/6	polymorphism

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: rs150191046; hg19: chr1-55118790; COSMIC: COSV100273998; COSMIC: COSV100273998;