17-36602169-G-C

Variant names:

• chr17-36602169-G-C
• rs78943308
• NM_024864.5:c.359G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024864.5(MRM1):​c.359G>C​(p.Cys120Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,612,390 control chromosomes in the GnomAD database, including 2,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (320 hom., cov: 32)
  • Exomes 𝑓: 0.053 (2589 hom.)
• Consequence: MRM1 NM_024864.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 8.48
• Publications: 17 publications found

Genes affected

MRM1 (HGNC:26202): (mitochondrial rRNA methyltransferase 1) Enables rRNA (guanosine-2'-O-)-methyltransferase activity. Predicted to be involved in rRNA 2'-O-methylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023248196).
• BP6: Variant 17-36602169-G-C is Benign according to our data. Variant chr17-36602169-G-C is described in ClinVar as [Benign]. Clinvar id is 1685657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRM1	NM_024864.5	c.359G>C	p.Cys120Ser	missense_variant	Exon 1 of 5	ENST00000614766.5	NP_079140.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRM1	ENST00000614766.5	c.359G>C	p.Cys120Ser	missense_variant	Exon 1 of 5	1	NM_024864.5	ENSP00000481559.1
MRM1	ENST00000612760.1	c.-51G>C		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000482526.1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7561 AN: 152146 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.00919

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0792

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0459

Gnomad OTH AF: 0.0560

GnomAD2 exomes AF: 0.0642 AC: 15668 AN: 244080 AF XY: 0.0648

Gnomad AFR exome AF: 0.00753

Gnomad AMR exome AF: 0.0433

Gnomad ASJ exome AF: 0.0629

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0471

Gnomad OTH exome AF: 0.0616

GnomAD4 exome AF: 0.0528 AC: 77047 AN: 1460126 Hom.: 2589 Cov.: 32 AF XY: 0.0533 AC XY: 38722 AN XY: 726142

African (AFR) AF: 0.00876 AC: 293 AN: 33456

American (AMR) AF: 0.0443 AC: 1982 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 1648 AN: 26128

East Asian (EAS) AF: 0.175 AC: 6940 AN: 39678

South Asian (SAS) AF: 0.0665 AC: 5733 AN: 86238

European-Finnish (FIN) AF: 0.126 AC: 6670 AN: 52796

Middle Eastern (MID) AF: 0.0662 AC: 377 AN: 5692

European-Non Finnish (NFE) AF: 0.0449 AC: 49851 AN: 1111152

Other (OTH) AF: 0.0589 AC: 3553 AN: 60286

GnomAD4 genome AF: 0.0497 AC: 7569 AN: 152264 Hom.: 320 Cov.: 32 AF XY: 0.0557 AC XY: 4143 AN XY: 74444

African (AFR) AF: 0.00916 AC: 381 AN: 41580

American (AMR) AF: 0.0617 AC: 944 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3470

East Asian (EAS) AF: 0.164 AC: 848 AN: 5168

South Asian (SAS) AF: 0.0788 AC: 380 AN: 4820

European-Finnish (FIN) AF: 0.133 AC: 1410 AN: 10612

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0459 AC: 3118 AN: 67990

Other (OTH) AF: 0.0578 AC: 122 AN: 2112

Alfa AF: 0.0515 Hom.: 207

Bravo AF: 0.0422

TwinsUK AF: 0.0410 AC: 152

ALSPAC AF: 0.0446 AC: 172

ESP6500AA AF: 0.00845 AC: 37

ESP6500EA AF: 0.0454 AC: 388

ExAC AF: 0.0597 AC: 7225

Asia WGS AF: 0.105 AC: 367 AN: 3478

EpiCase AF: 0.0516

EpiControl AF: 0.0503

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.5
PrimateAI	Pathogenic	0.81	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.97	D
Vest4		0.30
MutPred		0.74		Gain of disorder (P = 0.0228);
ClinPred		0.029	T
GERP RS		4.9
PromoterAI		0.061	Neutral
Varity_R		0.75
gMVP		0.80
Mutation Taster		=176/124	polymorphism (auto)

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: rs78943308; hg19: chr17-34958598;