2-178478467-G-C

Variant names:

• chr2-178478467-G-C
• NM_181342.3:c.33C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_181342.3(FKBP7):​c.33C>G​(p.Phe11Leu) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FKBP7 NM_181342.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.953

Genes affected

FKBP7 (HGNC:3723): (FKBP prolyl isomerase 7) The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. Members of this family exhibit PPIase activity and function as molecular chaperones. A similar protein in mouse is located in the endoplasmic reticulum and binds calcium. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04508072).
• BP6: Variant 2-178478467-G-C is Benign according to our data. Variant chr2-178478467-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3515537.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP7	NM_181342.3	c.33C>G	p.Phe11Leu	missense_variant	Exon 1 of 4	ENST00000424785.7	NP_851939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP7	ENST00000424785.7	c.33C>G	p.Phe11Leu	missense_variant	Exon 1 of 4	1	NM_181342.3	ENSP00000413152.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 13, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.37
DANN	Benign	0.60
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.58	N;N
REVEL	Benign	0.0070
Sift	Benign	0.74	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0	.;B
Vest4		0.13
MutPred		0.36		Gain of catalytic residue at F11 (P = 0.0632);Gain of catalytic residue at F11 (P = 0.0632);
MVP		0.16
MPC		0.075
ClinPred		0.023	T
GERP RS		-4.2
Varity_R		0.025
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-179343194;