Variant 16-4340872-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016069.11(PAM16):c.291+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,608,798 control chromosomes in the GnomAD database, including 5,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1058 hom., cov: 33)

Exomes 𝑓: 0.073 ( 4518 hom. )

Consequence

PAM16
NM_016069.11 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

PAM16 (HGNC:29679): (presequence translocase associated motor 16) This gene encodes a mitochondrial protein involved in granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. This protein also plays a role in the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix and may be important in reactive oxygen species (ROS) homeostasis. Mutations in this gene cause Megarbane-Dagher-Melike type spondylometaphyseal dysplasia, an early lethal skeletal dysplasia characterized by short stature, developmental delay and other skeletal abnormalities. [provided by RefSeq, May 2017]

PAM16 links:

CORO7-PAM16 (HGNC:44424): (CORO7-PAM16 readthrough) This locus represents naturally occurring read-through transcription between the neighboring CORO7 (coronin 7) and PAM16 (presequence translocase-associated motor 16) genes on chromosome 16. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2011]

CORO7-PAM16 links:

PAM16 (HGNC:):

PAM16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-4340872-A-G is Benign according to our data. Variant chr16-4340872-A-G is described in ClinVar as [Benign]. Clinvar id is 1244473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAM16	NM_016069.11 linkuse as main transcript	c.291+48T>C		intron_variant		ENST00000318059.8	NP_057153.8	Q9Y3D7
CORO7-PAM16	NM_001201479.2 linkuse as main transcript	c.3060+48T>C		intron_variant			NP_001188408.1	A0A0A6YYL4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAM16	ENST00000318059.8 linkuse as main transcript	c.291+48T>C		intron_variant		1	NM_016069.11	ENSP00000315693.3		Q9Y3D7
CORO7-PAM16	ENST00000572467.5 linkuse as main transcript	c.3060+48T>C		intron_variant		2		ENSP00000460885.1		A0A0A6YYL4

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15806

AN:

152088

Hom.:

1048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0756

Gnomad OTH

AF:

0.0990

GnomAD3 exomes

AF:

0.0753

AC:

18859

AN:

250382

Hom.:

975

AF XY:

0.0700

AC XY:

9500

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.180

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.0674

Gnomad EAS exome

AF:

0.00180

Gnomad SAS exome

AF:

0.0277

Gnomad FIN exome

AF:

0.0479

Gnomad NFE exome

AF:

0.0730

Gnomad OTH exome

AF:

0.0710

GnomAD4 exome

AF:

0.0730

AC:

106289

AN:

1456592

Hom.:

4518

Cov.:

AF XY:

0.0711

AC XY:

51576

AN XY:

724924

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.0694

Gnomad4 EAS exome

AF:

0.00232

Gnomad4 SAS exome

AF:

0.0272

Gnomad4 FIN exome

AF:

0.0505

Gnomad4 NFE exome

AF:

0.0741

Gnomad4 OTH exome

AF:

0.0750

GnomAD4 genome

AF:

0.104

AC:

15855

AN:

152206

Hom.:

1058

Cov.:

AF XY:

0.102

AC XY:

7600

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.0726

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0516

Gnomad4 NFE

AF:

0.0756

Gnomad4 OTH

AF:

0.0975

Alfa

AF:

0.0884

Hom.:

182

Bravo

AF:

0.115

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.8

DANN

Benign

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over