8-141477837-C-T

Variant names:

• chr8-141477837-C-T
• rs6997753
• ENST00000430863.5:c.1304G>A

Variant summary

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

The ENST00000430863.5(MROH5):​c.1304G>A​(p.Arg435Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 1,613,172 control chromosomes in the GnomAD database, including 667 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/10 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. R435L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.037 (341 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (326 hom.)
• Consequence: MROH5 ENST00000430863.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808
• Publications: 4 publications found

Genes affected

MROH5 (HGNC:42976): (maestro heat like repeat family member 5 (gene/pseudogene))

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018429458).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000430863.5. 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
	MROH5	NR_102363.3		n.1270G>A		non_coding_transcript_exon	Exon 10 of 28
	MROH5	NR_102364.3		n.1411G>A		non_coding_transcript_exon	Exon 11 of 27
	MROH5	NR_160399.1		n.1384G>A		non_coding_transcript_exon	Exon 11 of 30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH5	ENST00000430863.5	TSL:1	c.1304G>A	p.Arg435Gln	missense	Exon 11 of 30	ENSP00000431031.1
	MROH5	ENST00000521053.5	TSL:5	n.*1070G>A		non_coding_transcript_exon	Exon 10 of 28	ENSP00000429433.1	E5RFU7
	MROH5	ENST00000523857.5	TSL:2	n.*1211G>A		non_coding_transcript_exon	Exon 11 of 27	ENSP00000427945.1	E5RFU7

Frequencies

GnomAD3 genomes AF: 0.0370 AC: 5629 AN: 152128 Hom.: 343 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.0102 AC: 2541 AN: 248060 AF XY: 0.00788

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.00787

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.000703

Gnomad OTH exome AF: 0.00731

GnomAD4 exome AF: 0.00412 AC: 6019 AN: 1460926 Hom.: 326 Cov.: 33 AF XY: 0.00357 AC XY: 2595 AN XY: 726768

African (AFR) AF: 0.135 AC: 4528 AN: 33476

American (AMR) AF: 0.00776 AC: 347 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86244

European-Finnish (FIN) AF: 0.0000949 AC: 5 AN: 52712

Middle Eastern (MID) AF: 0.00919 AC: 53 AN: 5768

European-Non Finnish (NFE) AF: 0.000469 AC: 522 AN: 1111838

Other (OTH) AF: 0.00880 AC: 531 AN: 60362

GnomAD4 genome AF: 0.0370 AC: 5636 AN: 152246 Hom.: 341 Cov.: 32 AF XY: 0.0365 AC XY: 2720 AN XY: 74444

African (AFR) AF: 0.128 AC: 5296 AN: 41528

American (AMR) AF: 0.0146 AC: 223 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68018

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

Alfa AF: 0.0131 Hom.: 114

Bravo AF: 0.0432

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.124 AC: 522

ESP6500EA AF: 0.000826 AC: 7

ExAC AF: 0.0124 AC: 1504

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0018	T
PhyloP100		0.81
PrimateAI	Benign	0.28	T
Vest4		0.15
GERP RS		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6997753; hg19: chr8-142487937; COSMIC: COSV101435955;