16-1772286-T-C

Variant names:

• chr16-1772286-T-C
• rs746278949
• NM_023936.2:c.592A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_023936.2(MRPS34):​c.592A>G​(p.Met198Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,612,850 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (7 hom.)
• Consequence: MRPS34 NM_023936.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.11

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006157756).
• BP6: Variant 16-1772286-T-C is Benign according to our data. Variant chr16-1772286-T-C is described in ClinVar as [Benign]. Clinvar id is 3608637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS34	NM_023936.2	c.592A>G	p.Met198Val	missense_variant	Exon 3 of 3	ENST00000397375.7	NP_076425.1
MRPS34	NM_001300900.2	c.613A>G	p.Met205Val	missense_variant	Exon 3 of 3		NP_001287829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS34	ENST00000397375.7	c.592A>G	p.Met198Val	missense_variant	Exon 3 of 3	1	NM_023936.2	ENSP00000380531.3
MRPS34	ENST00000177742.7	c.613A>G	p.Met205Val	missense_variant	Exon 3 of 3	1		ENSP00000177742.3
MRPS34	ENST00000569585.1	n.323A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152238 Hom.: 0 Cov.: 33

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: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000244 AC: 61 AN: 250114 Hom.: 1 AF XY: 0.000339 AC XY: 46 AN XY: 135596

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 172 AN: 1460612 Hom.: 7 Cov.: 32 AF XY: 0.000182 AC XY: 132 AN XY: 726614

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00191

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74380

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.0000151

ExAC AF: 0.000247 AC: 30

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.046
DANN	Benign	0.66
DEOGEN2	Benign	0.0056	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.0062	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	.;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.0040
Sift	Benign	0.47	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0	B;B
Vest4		0.078
MutPred		0.24		Loss of disorder (P = 0.0543);.;
MVP		0.030
MPC		0.16
ClinPred		0.033	T
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.34

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: rs746278949; hg19: chr16-1822287;