NM_017946.4:c.601G>A

Variant names:

• chr7-30014770-C-T
• NM_017946.4:c.601G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017946.4(FKBP14):​c.601G>A​(p.Ala201Thr) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FKBP14 NM_017946.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18920276).

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.601G>A	p.Ala201Thr	missense	Exon 4 of 4	NP_060416.1	Q9NWM8
	FKBP14	NR_046478.2		n.887G>A		non_coding_transcript_exon	Exon 5 of 5
	FKBP14	NR_046479.2		n.643G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	ENST00000222803.10	TSL:1 MANE Select	c.601G>A	p.Ala201Thr	missense	Exon 4 of 4	ENSP00000222803.5	Q9NWM8
	FKBP14	ENST00000419018.1	TSL:1	n.*248G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000406270.1	F8WBZ0
	FKBP14	ENST00000419018.1	TSL:1	n.*248G>A		3_prime_UTR	Exon 3 of 3	ENSP00000406270.1	F8WBZ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Benign	0.82
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.092
Sift	Benign	0.55	T
Sift4G	Benign	0.74	T
Polyphen		0.074	B
Vest4		0.14
MutPred		0.26		Gain of glycosylation at A201 (P = 0.0453)
MVP		0.78
MPC		0.11
ClinPred		0.72	D
GERP RS		5.0
Varity_R		0.22
gMVP		0.39
Mutation Taster		=40/60	disease causing

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

hg19: chr7-30054386;