rs8115854

Variant names:

• chr20-37137934-A-G
• rs8115854
• NM_152503.8:c.1525T>C

Variant summary

Our verdict is Benign. The variant received -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. 12/15 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MROH8	NM_152503.8	c.1525T>C	p.Ser509Pro	missense_variant	Exon 13 of 25	ENST00000710289.2	NP_689716.4
MROH8	NM_213631.3	c.1525T>C	p.Ser509Pro	missense_variant	Exon 13 of 14		NP_998796.1
MROH8	NM_213632.3	c.1420T>C	p.Ser474Pro	missense_variant	Exon 12 of 13		NP_998797.2

Ensembl

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

GnomAD2 exomes AF: 0.300 AC: 74539 AN: 248174 AF XY: 0.303

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 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

African (AFR) AF: 0.523 AC: 13750 AN: 26294

American (AMR) AF: 0.187 AC: 6946 AN: 37226

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 5860 AN: 16876

East Asian (EAS) AF: 0.00661 AC: 111 AN: 16804

South Asian (SAS) AF: 0.263 AC: 21845 AN: 83124

European-Finnish (FIN) AF: 0.311 AC: 10132 AN: 32556

Middle Eastern (MID) AF: 0.407 AC: 1822 AN: 4472

European-Non Finnish (NFE) AF: 0.354 AC: 337257 AN: 953042

Other (OTH) AF: 0.336 AC: 14792 AN: 43972

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

African (AFR) AF: 0.520 AC: 21556 AN: 41454

American (AMR) AF: 0.268 AC: 4091 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1198 AN: 3462

East Asian (EAS) AF: 0.00984 AC: 51 AN: 5184

South Asian (SAS) AF: 0.248 AC: 1195 AN: 4816

European-Finnish (FIN) AF: 0.307 AC: 3245 AN: 10576

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24325 AN: 67990

Other (OTH) AF: 0.375 AC: 792 AN: 2110

Alfa AF: 0.356 Hom.: 43903

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
PhyloP100		0.34
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
Mutation Taster		=96/4	polymorphism (auto)

Splicing

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

Other links and lift over

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