chr20-37137934-A-G

Position:

• chr20-37137934-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152503.8(MROH8):​c.1525T>C​(p.Ser509Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,366,412 control chromosomes in the GnomAD database, including 84,367 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 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: 𝑓 0.37 (11600 hom., cov: 32)
  • Exomes 𝑓: 0.34 (72767 hom.)
• Consequence: MROH8 NM_152503.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

Genes affected

MROH8 (HGNC:16125): (maestro heat like repeat family member 8) The protein encoded by this gene belongs to the maestro heat-like repeat family. The exact function of this gene is not known, however, in a genome-wide association study using hippocampal atrophy as a quantitative trait, this gene has been associated with Alzheimer's disease (PMID:19668339). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.7787806E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH8	NM_152503.8	c.1525T>C	p.Ser509Pro	missense_variant	13/25		NP_689716.4
MROH8	NM_213631.3	c.1525T>C	p.Ser509Pro	missense_variant	13/14		NP_998796.1
MROH8	NM_213632.3	c.1420T>C	p.Ser474Pro	missense_variant	12/13		NP_998797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10	c.1525T>C	p.Ser509Pro	missense_variant	13/25	1		ENSP00000513568.1
MROH8	ENST00000400440.7	c.1525T>C	p.Ser509Pro	missense_variant	13/14	1		ENSP00000513569.1
MROH8	ENST00000422138.2	c.1267T>C	p.Ser423Pro	missense_variant	11/23	3		ENSP00000400468.2
MROH8	ENST00000421643.2	c.1420T>C	p.Ser474Pro	missense_variant	12/13	2		ENSP00000513570.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56818 AN: 151928 Hom.: 11588 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.380

GnomAD3 exomes AF: 0.300 AC: 74539 AN: 248174 Hom.: 12880 AF XY: 0.303 AC XY: 40814 AN XY: 134586

Gnomad AFR exome AF: 0.519

Gnomad AMR exome AF: 0.184

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.00596

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.355

Gnomad OTH exome AF: 0.335

GnomAD4 exome AF: 0.340 AC: 412515 AN: 1214366 Hom.: 72767 Cov.: 33 AF XY: 0.337 AC XY: 202977 AN XY: 601744

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.00661

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.374 AC: 56855 AN: 152046 Hom.: 11600 Cov.: 32 AF XY: 0.367 AC XY: 27258 AN XY: 74330

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.00984

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.375

Alfa AF: 0.353 Hom.: 20620

Bravo AF: 0.377

TwinsUK AF: 0.353 AC: 1308

ALSPAC AF: 0.357 AC: 1375

ESP6500AA AF: 0.503 AC: 1874

ESP6500EA AF: 0.365 AC: 2995

ExAC AF: 0.308 AC: 37248

Asia WGS AF: 0.162 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Benign	0.94
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.000038	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.19
Sift	Benign	0.27	T
Sift4G	Benign	0.44	T
Polyphen		0.0010	B
Vest4		0.062
ClinPred		0.0038	T
GERP RS		0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8115854; hg19: chr20-35766337; COSMIC: COSV54119063;