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

Variant names:

• chr16-4340913-C-A
• rs142976385
• NM_016069.11:c.291+7G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_016069.11(PAM16):​c.291+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,612,938 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (35 hom.)
• Consequence: PAM16 NM_016069.11 splice_region, intron
• Scores: Splicing: ADA: 0.0008855
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.354
• Publications: 0 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 16-4340913-C-A is Benign according to our data. Variant chr16-4340913-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 789224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 35 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016069.11. 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
	PAM16	NM_016069.11	MANE Select	c.291+7G>T		splice_region intron	N/A	NP_057153.8
	CORO7-PAM16	NM_001201479.2		c.3060+7G>T		splice_region intron	N/A	NP_001188408.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAM16	ENST00000318059.8	TSL:1 MANE Select	c.291+7G>T		splice_region intron	N/A	ENSP00000315693.3	Q9Y3D7
	CORO7-PAM16	ENST00000572467.5	TSL:2	c.3060+7G>T		splice_region intron	N/A	ENSP00000460885.1
	PAM16	ENST00000573236.5	TSL:1	n.547+7G>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 644 AN: 152094 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00718

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00390 AC: 979 AN: 250954 AF XY: 0.00395

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.0117

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00240

Gnomad NFE exome AF: 0.00598

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00572 AC: 8354 AN: 1460728 Hom.: 35 Cov.: 32 AF XY: 0.00558 AC XY: 4051 AN XY: 726614

African (AFR) AF: 0.00105 AC: 35 AN: 33456

American (AMR) AF: 0.00135 AC: 60 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 327 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00129 AC: 111 AN: 86250

European-Finnish (FIN) AF: 0.00286 AC: 151 AN: 52838

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00664 AC: 7379 AN: 1111680

Other (OTH) AF: 0.00480 AC: 290 AN: 60370

GnomAD4 genome AF: 0.00422 AC: 643 AN: 152210 Hom.: 1 Cov.: 33 AF XY: 0.00369 AC XY: 275 AN XY: 74438

African (AFR) AF: 0.00125 AC: 52 AN: 41548

American (AMR) AF: 0.00124 AC: 19 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00716 AC: 487 AN: 67986

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00621 Hom.: 2

Bravo AF: 0.00387

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00594

EpiControl AF: 0.00557

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	PAM16-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.2
DANN	Benign	0.86
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00089
dbscSNV1_RF	Benign	0.026
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: rs142976385; hg19: chr16-4390914;