chr9-113162652-C-G

Position:

• chr9-113162652-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015258.2(FKBP15):​c.*3426G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 1,126,300 control chromosomes in the GnomAD database, including 601 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.036 (137 hom., cov: 31)
  • Exomes 𝑓: 0.027 (464 hom.)
• Consequence: FKBP15 NM_015258.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

Genes affected

FKBP15 (HGNC:23397): (FKBP prolyl isomerase family member 15) Predicted to enable actin binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in endocytosis and protein peptidyl-prolyl isomerization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC31A2 (HGNC:11017): (solute carrier family 31 member 2) Predicted to enable copper ion transmembrane transporter activity. Predicted to be involved in cellular copper ion homeostasis. Predicted to act upstream of or within regulation of copper ion transmembrane transport. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FKBP15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP15	NM_015258.2	c.*3426G>C		3_prime_UTR_variant	28/28	ENST00000238256.8	NP_056073.1
SLC31A2	NM_001860.3	c.264-97C>G		intron_variant		ENST00000259392.8	NP_001851.1
FKBP15	XM_006717018.3	c.*3426G>C		3_prime_UTR_variant	28/28		XP_006717081.1
FKBP15	XM_006717019.2	c.*3426G>C		3_prime_UTR_variant	27/27		XP_006717082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP15	ENST00000238256	c.*3426G>C		3_prime_UTR_variant	28/28	1	NM_015258.2	ENSP00000238256.3
SLC31A2	ENST00000259392.8	c.264-97C>G		intron_variant		1	NM_001860.3	ENSP00000259392.3

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5505 AN: 152022 Hom.: 137 Cov.: 31

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0759

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0273 AC: 26583 AN: 974160 Hom.: 464 Cov.: 12 AF XY: 0.0273 AC XY: 13455 AN XY: 493046

Gnomad4 AFR exome AF: 0.0553

Gnomad4 AMR exome AF: 0.0262

Gnomad4 ASJ exome AF: 0.0726

Gnomad4 EAS exome AF: 0.00138

Gnomad4 SAS exome AF: 0.0198

Gnomad4 FIN exome AF: 0.00612

Gnomad4 NFE exome AF: 0.0280

Gnomad4 OTH exome AF: 0.0310

GnomAD4 genome AF: 0.0362 AC: 5513 AN: 152140 Hom.: 137 Cov.: 31 AF XY: 0.0345 AC XY: 2563 AN XY: 74370

Gnomad4 AFR AF: 0.0594

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0759

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0196

Gnomad4 FIN AF: 0.00462

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0302 Hom.: 8

Bravo AF: 0.0396

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs10513187; hg19: chr9-115924932;