1-170971808-C-T

Variant names:

• chr1-170971808-C-T
• rs1182601623
• NM_001163629.2:c.541C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001163629.2(MROH9):​c.541C>T​(p.His181Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: MROH9 NM_001163629.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

Genes affected

MROH9 (HGNC:26287): (maestro heat like repeat family member 9)

ENSG00000231424 (HGNC:40240):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4119631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH9	NM_001163629.2	c.541C>T	p.His181Tyr	missense_variant	Exon 8 of 22	ENST00000367759.9	NP_001157101.1
MROH9	NM_025063.4	c.541C>T	p.His181Tyr	missense_variant	Exon 8 of 15		NP_079339.2
MROH9	XM_011510005.3	c.541C>T	p.His181Tyr	missense_variant	Exon 8 of 21		XP_011508307.1
MROH9	XM_011510006.3	c.541C>T	p.His181Tyr	missense_variant	Exon 8 of 21		XP_011508308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH9	ENST00000367759.9	c.541C>T	p.His181Tyr	missense_variant	Exon 8 of 22	5	NM_001163629.2	ENSP00000356733.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461762 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.541C>T (p.H181Y) alteration is located in exon 8 (coding exon 7) of the MROH9 gene. This alteration results from a C to T substitution at nucleotide position 541, causing the histidine (H) at amino acid position 181 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.063	.;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.093
Sift	Benign	0.12	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.49	.;P
Vest4		0.52
MutPred		0.60		Loss of disorder (P = 0.0555);Loss of disorder (P = 0.0555);
MVP		0.18
MPC		0.25
ClinPred		0.40	T
GERP RS		4.3
Varity_R		0.085
gMVP		0.20

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: rs1182601623; hg19: chr1-170940949;