rs10513187

Variant names:

• chr9-113162652-C-A
• rs10513187
• NM_015258.2:c.*3426G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-113162652-C-A
• chr9-113162652-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015258.2(FKBP15):​c.*3426G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 974,432 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: FKBP15 NM_015258.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP15	NM_015258.2	c.*3426G>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000238256.8	NP_056073.1
SLC31A2	NM_001860.3	c.264-97C>A		intron_variant	Intron 3 of 3	ENST00000259392.8	NP_001851.1
FKBP15	XM_006717018.3	c.*3426G>T		3_prime_UTR_variant	Exon 28 of 28		XP_006717081.1
FKBP15	XM_006717019.2	c.*3426G>T		3_prime_UTR_variant	Exon 27 of 27		XP_006717082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP15	ENST00000238256.8	c.*3426G>T		3_prime_UTR_variant	Exon 28 of 28	1	NM_015258.2	ENSP00000238256.3
SLC31A2	ENST00000259392.8	c.264-97C>A		intron_variant	Intron 3 of 3	1	NM_001860.3	ENSP00000259392.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000103 AC: 1 AN: 974432 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 493182

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22792

American (AMR) AF: 0.00 AC: 0 AN: 32756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18150

East Asian (EAS) AF: 0.00 AC: 0 AN: 35454

South Asian (SAS) AF: 0.00 AC: 0 AN: 63414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3418

European-Non Finnish (NFE) AF: 0.00000140 AC: 1 AN: 714362

Other (OTH) AF: 0.00 AC: 0 AN: 43534

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.62
PhyloP100		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10513187; hg19: chr9-115924932;