6-122781099-G-A

Variant names:

• chr6-122781099-G-A
• NM_001446.5:c.253G>A

Variant summary

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

The NM_001446.5(FABP7):​c.253G>A​(p.Val85Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FABP7 NM_001446.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02
• Publications: 0 publications found

Genes affected

FABP7 (HGNC:3562): (fatty acid binding protein 7) The gene encodes a small, highly conserved cytoplasmic protein that bind long-chain fatty acids and other hydrophobic ligands. The encoded protein is important in the establishment of the radial glial fiber in the developing brain. Alternative splicing and promoter usage results in multiple transcript variants encoding different isoforms. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Jan 2016]

ENSG00000294893 (HGNC:):

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=0.12558606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001446.5. 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
	FABP7	NM_001446.5	MANE Select	c.253G>A	p.Val85Ile	missense	Exon 3 of 4	NP_001437.1	O15540-1
	FABP7	NM_001319039.2		c.253G>A	p.Val85Ile	missense	Exon 3 of 3	NP_001305968.1	O15540-2
	FABP7	NM_001319042.2		c.241G>A	p.Val81Ile	missense	Exon 3 of 4	NP_001305971.1	A0A077H155

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FABP7	ENST00000368444.8	TSL:1 MANE Select	c.253G>A	p.Val85Ile	missense	Exon 3 of 4	ENSP00000357429.3	O15540-1
	FABP7	ENST00000356535.4	TSL:1	c.253G>A	p.Val85Ile	missense	Exon 3 of 3	ENSP00000348931.4	O15540-2
	ENSG00000294893	ENST00000726593.1		n.569C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.059
Sift	Benign	0.43	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.60		Gain of ubiquitination at K82 (P = 0.1181)
MVP		0.45
MPC		0.17
ClinPred		0.37	T
GERP RS		1.1
Varity_R		0.071
gMVP		0.28
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-123102244;