8-81529463-A-G

Position:

• chr8-81529463-A-G

Variant summary

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

The NM_001105281.6(FABP12):​c.221T>C​(p.Ile74Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FABP12 NM_001105281.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.757

Genes affected

FABP12 (HGNC:34524): (fatty acid binding protein 12) Predicted to enable lipid binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

FABP12 (HGNC:):

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=0.029852927).
• BP6: Variant 8-81529463-A-G is Benign according to our data. Variant chr8-81529463-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2249992.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP12	NM_001105281.6	c.221T>C	p.Ile74Thr	missense_variant	3/5		NP_001098751.1
FABP12	XM_006716465.4	c.221T>C	p.Ile74Thr	missense_variant	3/5		XP_006716528.1
FABP12	XM_011517577.3	c.221T>C	p.Ile74Thr	missense_variant	4/6		XP_011515879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP12	ENST00000360464.6	c.221T>C	p.Ile74Thr	missense_variant	3/5	1		ENSP00000353650.4
FABP12	ENST00000692030.1	c.221T>C	p.Ile74Thr	missense_variant	4/6			ENSP00000510293.1
FABP12	ENST00000519696.1	n.173T>C		non_coding_transcript_exon_variant	2/4	5		ENSP00000427973.1
ENSG00000253374	ENST00000523380.5	n.505+3007A>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

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	0.067
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.47
DANN	Benign	0.68
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.6	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	3.7	N
REVEL	Benign	0.058
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.31		Loss of catalytic residue at P76 (P = 0.0374);
MVP		0.014
MPC		0.0091
ClinPred		0.045	T
GERP RS		-0.051
Varity_R		0.035
gMVP		0.17

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: chr8-82441698;