16-4340417-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016069.11(PAM16):​c.292-12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,609,016 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 Benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

PAM16
NM_016069.11 intron

Scores

2
Splicing: ADA: 0.0001357
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.565
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 16-4340417-C-T is Benign according to our data. Variant chr16-4340417-C-T is described in ClinVar as [Benign]. Clinvar id is 1990304.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAM16NM_016069.11 linkc.292-12G>A intron_variant Intron 4 of 4 ENST00000318059.8 NP_057153.8 Q9Y3D7
CORO7-PAM16NM_001201479.2 linkc.3061-12G>A intron_variant Intron 30 of 30 NP_001188408.1 A0A0A6YYL4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAM16ENST00000318059.8 linkc.292-12G>A intron_variant Intron 4 of 4 1 NM_016069.11 ENSP00000315693.3 Q9Y3D7
CORO7-PAM16ENST00000572467.5 linkc.3061-12G>A intron_variant Intron 30 of 30 2 ENSP00000460885.1 A0A0A6YYL4

Frequencies

GnomAD3 genomes
AF:
0.000578
AC:
88
AN:
152160
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00198
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000179
AC:
44
AN:
245868
Hom.:
1
AF XY:
0.0000673
AC XY:
9
AN XY:
133798
show subpopulations
Gnomad AFR exome
AF:
0.00214
Gnomad AMR exome
AF:
0.0000583
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000452
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000113
AC:
164
AN:
1456738
Hom.:
1
Cov.:
33
AF XY:
0.0000966
AC XY:
70
AN XY:
724408
show subpopulations
Gnomad4 AFR exome
AF:
0.00230
Gnomad4 AMR exome
AF:
0.0000450
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000549
Gnomad4 OTH exome
AF:
0.000266
GnomAD4 genome
AF:
0.000578
AC:
88
AN:
152278
Hom.:
0
Cov.:
33
AF XY:
0.000537
AC XY:
40
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00197
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000434
Hom.:
0
Bravo
AF:
0.000892
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 21, 2025
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
BayesDel_noAF
Benign
-0.86
CADD
Benign
5.3
DANN
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00014
dbscSNV1_RF
Benign
0.028
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.

Other links and lift over

dbSNP: rs200459458; hg19: chr16-4390418; API