NM_016069.11:c.291+7G>A

Variant names:

• chr16-4340913-C-T
• NM_016069.11:c.291+7G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016069.11(PAM16):​c.291+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PAM16 NM_016069.11 splice_region, intron
• Scores: Splicing: ADA: 0.002073
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAM16	NM_016069.11	c.291+7G>A		splice_region_variant, intron_variant	Intron 4 of 4	ENST00000318059.8	NP_057153.8
CORO7-PAM16	NM_001201479.2	c.3060+7G>A		splice_region_variant, intron_variant	Intron 30 of 30		NP_001188408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAM16	ENST00000318059.8	c.291+7G>A		splice_region_variant, intron_variant	Intron 4 of 4	1	NM_016069.11	ENSP00000315693.3
CORO7-PAM16	ENST00000572467.5	c.3060+7G>A		splice_region_variant, intron_variant	Intron 30 of 30	2		ENSP00000460885.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460744 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726622

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.8
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.016
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-4390914;