7-30019098-C-A

Variant names:

• chr7-30019098-C-A
• NM_017946.4:c.375G>T
• FKBP14 p.Leu125Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017946.4(FKBP14):​c.375G>T​(p.Leu125Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L125L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FKBP14 NM_017946.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• Publications: 0 publications found

Genes affected

FKBP14 (HGNC:18625): (FKBP prolyl isomerase 14) The protein encoded by this gene is a member of the FK506-binding protein family of peptidyl-prolyl cis-trans isomerases. The encoded protein is found in the lumen of the endoplasmic reticulum, where it is thought to accelerate protein folding. Defects in this gene are a cause of a type of Ehlers-Danlos syndrome (EDS). Both a protein-coding variant and noncoding variants are transcribed from this gene. [provided by RefSeq, Mar 2012]

FKBP14-AS1 (HGNC:40990): (FKBP14 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.776 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017946.4. 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
	FKBP14	NM_017946.4	MANE Select	c.375G>T	p.Leu125Leu	synonymous	Exon 3 of 4	NP_060416.1	Q9NWM8
	FKBP14	NR_046478.2		n.661G>T		non_coding_transcript_exon	Exon 4 of 5
	FKBP14	NR_046479.2		n.417G>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	ENST00000222803.10	TSL:1 MANE Select	c.375G>T	p.Leu125Leu	synonymous	Exon 3 of 4	ENSP00000222803.5	Q9NWM8
	FKBP14	ENST00000419018.1	TSL:1	n.*22G>T		non_coding_transcript_exon	Exon 2 of 3	ENSP00000406270.1	F8WBZ0
	FKBP14	ENST00000419018.1	TSL:1	n.*22G>T		3_prime_UTR	Exon 2 of 3	ENSP00000406270.1	F8WBZ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	10
DANN	Benign	0.78
PhyloP100		0.78

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-30058714;