rs1056386574

Variant names:

• chr16-1772844-C-G
• rs1056386574
• NM_023936.2:c.276G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-1772844-C-G
• chr16-1772844-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_023936.2(MRPS34):​c.276G>C​(p.Pro92Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000901 in 1,443,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 35)
  • Exomes 𝑓: 0.0000062 (1 hom.)
• Consequence: MRPS34 NM_023936.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.452
• Publications: 0 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]

EME2 (HGNC:27289): (essential meiotic structure-specific endonuclease subunit 2) EME2 forms a heterodimer with MUS81 (MIM 606591) that functions as an XPF (MIM 278760)-type flap/fork endonuclease in DNA repair (Ciccia et al., 2007 [PubMed 17289582]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 16-1772844-C-G is Benign according to our data. Variant chr16-1772844-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2973030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.452 with no splicing effect.

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.276G>C	p.Pro92Pro	synonymous	Exon 1 of 3	NP_076425.1	P82930
	EME2	NM_001257370.2	MANE Select	c.-384C>G		5_prime_UTR	Exon 1 of 8	NP_001244299.1	A4GXA9-1
	MRPS34	NM_001300900.2		c.276G>C	p.Pro92Pro	synonymous	Exon 1 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.276G>C	p.Pro92Pro	synonymous	Exon 1 of 3	ENSP00000380531.3	P82930
	MRPS34	ENST00000177742.7	TSL:1	c.276G>C	p.Pro92Pro	synonymous	Exon 1 of 3	ENSP00000177742.3	C9JJ19
	EME2	ENST00000568449.7	TSL:1 MANE Select	c.-384C>G		5_prime_UTR	Exon 1 of 8	ENSP00000457353.1	A4GXA9-1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152234 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 1 AN: 61998 AF XY: 0.00

Gnomad AFR exome AF: 0.000182

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 8 AN: 1291364 Hom.: 1 Cov.: 61 AF XY: 0.00000797 AC XY: 5 AN XY: 627402

African (AFR) AF: 0.000281 AC: 8 AN: 28490

American (AMR) AF: 0.00 AC: 0 AN: 21150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19090

East Asian (EAS) AF: 0.00 AC: 0 AN: 34508

South Asian (SAS) AF: 0.00 AC: 0 AN: 64880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1035378

Other (OTH) AF: 0.00 AC: 0 AN: 53628

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152234 Hom.: 0 Cov.: 35 AF XY: 0.0000403 AC XY: 3 AN XY: 74368

African (AFR) AF: 0.000121 AC: 5 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.45
PromoterAI		-0.0012	Neutral

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: rs1056386574; hg19: chr16-1822845;