rs6997753

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-141477837-C-A
• chr8-141477837-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MROH5 ENST00000430863.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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>T		non_coding_transcript_exon	Exon 10 of 28
	MROH5	NR_102364.3		n.1411G>T		non_coding_transcript_exon	Exon 11 of 27
	MROH5	NR_160399.1		n.1384G>T		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>T	p.Arg435Leu	missense	Exon 11 of 30	ENSP00000431031.1
	MROH5	ENST00000521053.5	TSL:5	n.*1070G>T		non_coding_transcript_exon	Exon 10 of 28	ENSP00000429433.1	E5RFU7
	MROH5	ENST00000523857.5	TSL:2	n.*1211G>T		non_coding_transcript_exon	Exon 11 of 27	ENSP00000427945.1	E5RFU7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248060 AF XY: 0.0000148

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
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
PhyloP100		0.81
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

Other links and lift over

dbSNP: rs6997753; hg19: chr8-142487937;