NM_016069.11:c.291+10C>T

Variant names:

• chr16-4340910-G-A
• rs116657149
• NM_016069.11:c.291+10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016069.11(PAM16):​c.291+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,612,954 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (53 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (78 hom.)
• Consequence: PAM16 NM_016069.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.138
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 16-4340910-G-A is Benign according to our data. Variant chr16-4340910-G-A is described in ClinVar as Benign. ClinVar VariationId is 783731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

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+10C>T		intron	N/A	NP_057153.8
	CORO7-PAM16	NM_001201479.2		c.3060+10C>T		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+10C>T		intron	N/A	ENSP00000315693.3	Q9Y3D7
	CORO7-PAM16	ENST00000572467.5	TSL:2	c.3060+10C>T		intron	N/A	ENSP00000460885.1
	PAM16	ENST00000573236.5	TSL:1	n.547+10C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2258 AN: 152050 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00408 AC: 1025 AN: 250948 AF XY: 0.00308

Gnomad AFR exome AF: 0.0522

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00173 AC: 2526 AN: 1460786 Hom.: 78 Cov.: 32 AF XY: 0.00150 AC XY: 1090 AN XY: 726648

African (AFR) AF: 0.0563 AC: 1885 AN: 33460

American (AMR) AF: 0.00348 AC: 155 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52816

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5766

European-Non Finnish (NFE) AF: 0.000204 AC: 227 AN: 1111746

Other (OTH) AF: 0.00374 AC: 226 AN: 60372

GnomAD4 genome AF: 0.0149 AC: 2264 AN: 152168 Hom.: 53 Cov.: 33 AF XY: 0.0142 AC XY: 1054 AN XY: 74416

African (AFR) AF: 0.0518 AC: 2149 AN: 41524

American (AMR) AF: 0.00393 AC: 60 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 67978

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00869 Hom.: 14

Bravo AF: 0.0168

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.4
DANN	Benign	0.77
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs116657149; hg19: chr16-4390911;