chr7-103297673-C-T

Variant names:

• chr7-103297673-C-T
• rs192846145
• NM_004279.3:c.99+115C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004279.3(PMPCB):​c.99+115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,541,956 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (13 hom., cov: 33)
  • Exomes 𝑓: 0.014 (165 hom.)
• Consequence: PMPCB NM_004279.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.76
• Publications: 2 publications found

Genes affected

PMPCB (HGNC:9119): (peptidase, mitochondrial processing subunit beta) This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex. [provided by RefSeq, Jul 2008]

PMPCB Gene-Disease associations (from GenCC):

• multiple mitochondrial dysfunctions syndrome 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-103297673-C-T is Benign according to our data. Variant chr7-103297673-C-T is described in ClinVar as Benign. ClinVar VariationId is 1701532.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00887 (1350/152252) while in subpopulation NFE AF = 0.0139 (948/68002). AF 95% confidence interval is 0.0132. There are 13 homozygotes in GnomAd4. There are 661 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004279.3. 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
	PMPCB	NM_004279.3	MANE Select	c.99+115C>T		intron	N/A	NP_004270.2	O75439
	PMPCB	NM_001438231.1		c.99+115C>T		intron	N/A	NP_001425160.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMPCB	ENST00000249269.9	TSL:1 MANE Select	c.99+115C>T		intron	N/A	ENSP00000249269.4	O75439
	PMPCB	ENST00000428154.5	TSL:1	c.99+115C>T		intron	N/A	ENSP00000390035.1	G3V0E4
	PMPCB	ENST00000706454.1		c.99+115C>T		intron	N/A	ENSP00000516392.1	A0A9L9PXI7

Frequencies

GnomAD3 genomes AF: 0.00887 AC: 1350 AN: 152134 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00888 AC: 1256 AN: 141368 AF XY: 0.00975

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.00229

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0126

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.00693

GnomAD4 exome AF: 0.0139 AC: 19273 AN: 1389704 Hom.: 165 Cov.: 31 AF XY: 0.0137 AC XY: 9392 AN XY: 685934

African (AFR) AF: 0.00227 AC: 72 AN: 31672

American (AMR) AF: 0.00258 AC: 92 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.00219 AC: 55 AN: 25130

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35818

South Asian (SAS) AF: 0.00818 AC: 646 AN: 79002

European-Finnish (FIN) AF: 0.0141 AC: 548 AN: 38836

Middle Eastern (MID) AF: 0.00193 AC: 11 AN: 5686

European-Non Finnish (NFE) AF: 0.0160 AC: 17256 AN: 1079884

Other (OTH) AF: 0.0102 AC: 592 AN: 57966

GnomAD4 genome AF: 0.00887 AC: 1350 AN: 152252 Hom.: 13 Cov.: 33 AF XY: 0.00888 AC XY: 661 AN XY: 74428

African (AFR) AF: 0.00214 AC: 89 AN: 41562

American (AMR) AF: 0.00229 AC: 35 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00706 AC: 34 AN: 4818

European-Finnish (FIN) AF: 0.0124 AC: 132 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 948 AN: 68002

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00976 Hom.: 0

Bravo AF: 0.00820

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
AlphaMissense	Benign	0.29
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.49
DANN	Benign	0.86
PhyloP100		-4.8
PromoterAI		-0.032	Neutral
Mutation Taster		=100/0	polymorphism

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: rs192846145; hg19: chr7-102938120;