16-1772158-T-C

Variant names:

• chr16-1772158-T-C
• rs2269123
• NM_023936.2:c.*63A>G

Variant summary

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

The NM_023936.2(MRPS34):​c.*63A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,500,538 control chromosomes in the GnomAD database, including 13,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1040 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12808 hom.)
• Consequence: MRPS34 NM_023936.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46
• Publications: 19 publications found

Genes affected

MRPS34 (HGNC:16618): (mitochondrial ribosomal protein S34) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MRPS34 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 32

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-1772158-T-C is Benign according to our data. Variant chr16-1772158-T-C is described in ClinVar as Benign. ClinVar VariationId is 1221216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023936.2. 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
	MRPS34	NM_023936.2	MANE Select	c.*63A>G		3_prime_UTR	Exon 3 of 3	NP_076425.1	P82930
	MRPS34	NM_001300900.2		c.*63A>G		3_prime_UTR	Exon 3 of 3	NP_001287829.1	C9JJ19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS34	ENST00000397375.7	TSL:1 MANE Select	c.*63A>G		3_prime_UTR	Exon 3 of 3	ENSP00000380531.3	P82930
	MRPS34	ENST00000177742.7	TSL:1	c.*63A>G		3_prime_UTR	Exon 3 of 3	ENSP00000177742.3	C9JJ19
	MRPS34	ENST00000890485.1		c.*63A>G		3_prime_UTR	Exon 3 of 3	ENSP00000560544.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16466 AN: 152078 Hom.: 1043 Cov.: 33

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.129 AC: 174407 AN: 1348342 Hom.: 12808 Cov.: 22 AF XY: 0.132 AC XY: 88020 AN XY: 667910

African (AFR) AF: 0.0459 AC: 1403 AN: 30594

American (AMR) AF: 0.0807 AC: 3032 AN: 37572

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 2048 AN: 22562

East Asian (EAS) AF: 0.299 AC: 11614 AN: 38808

South Asian (SAS) AF: 0.197 AC: 15511 AN: 78610

European-Finnish (FIN) AF: 0.151 AC: 5532 AN: 36596

Middle Eastern (MID) AF: 0.105 AC: 557 AN: 5330

European-Non Finnish (NFE) AF: 0.123 AC: 127863 AN: 1042040

Other (OTH) AF: 0.122 AC: 6847 AN: 56230

GnomAD4 genome AF: 0.108 AC: 16455 AN: 152196 Hom.: 1040 Cov.: 33 AF XY: 0.111 AC XY: 8231 AN XY: 74400

African (AFR) AF: 0.0485 AC: 2017 AN: 41550

American (AMR) AF: 0.107 AC: 1636 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1270 AN: 5152

South Asian (SAS) AF: 0.200 AC: 962 AN: 4810

European-Finnish (FIN) AF: 0.151 AC: 1604 AN: 10600

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8357 AN: 67988

Other (OTH) AF: 0.100 AC: 212 AN: 2112

Alfa AF: 0.111 Hom.: 1255

Bravo AF: 0.100

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.57
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs2269123; hg19: chr16-1822159; COSMIC: COSV51600716; COSMIC: COSV51600716;