rs6997753

chr8-141477837-C-Achr8-141477837-C-T

Variant summary

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

The ENST00000430863.5(MROH5):c.1304G>T(p.Arg435Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,928 control chromosomes in the GnomAD database, with no homozygous occurrence. 6/9 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MROH5 ENST00000430863.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH5	NR_102363.3	n.1270G>T		non_coding_transcript_exon_variant	10/28
MROH5	NR_102364.3	n.1411G>T		non_coding_transcript_exon_variant	11/27
MROH5	NR_160399.1	n.1384G>T		non_coding_transcript_exon_variant	11/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH5	ENST00000430863.5	c.1304G>T	p.Arg435Leu	missense_variant	11/30	1		P5
MROH5	ENST00000521053.5	c.*1070G>T		3_prime_UTR_variant, NMD_transcript_variant	10/28	5		A2
MROH5	ENST00000523857.5	c.*1211G>T		3_prime_UTR_variant, NMD_transcript_variant	11/27	2		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 248060 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460928 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

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.: 32

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	18
Dann	Uncertain	1.0
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.66	T
MetaRNN	Uncertain	0.50	D
PrimateAI	Benign	0.32	T
Vest4		0.62
MVP		0.16
GERP RS		2.4

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

LitVar

Other links and lift over

dbSNP: rs6997753; hg19: chr8-142487937;