chr6-122779865-T-C

Position:

chr6-122779865-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000368444.8(FABP7):c.71T>C(p.Leu24Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,282 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000046 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

FABP7
ENST00000368444.8 missense, splice_region

Scores

Splicing: ADA: 0.6860

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.95

Variant links:

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]

FABP7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FABP7	NM_001446.5 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant, splice_region_variant	1/4	ENST00000368444.8	NP_001437.1
FABP7	NM_001319039.2 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant, splice_region_variant	1/3		NP_001305968.1
FABP7	NM_001319041.2 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant, splice_region_variant	1/2		NP_001305970.1
FABP7	NM_001319042.2 linkuse as main transcript	c.62-426T>C		intron_variant			NP_001305971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP7	ENST00000368444.8 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant, splice_region_variant	1/4	1	NM_001446.5	ENSP00000357429	P1	O15540-1
FABP7	ENST00000356535.4 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant, splice_region_variant	1/3	1		ENSP00000348931		O15540-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251148

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000949

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1460992

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000824

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.71T>C (p.L24P) alteration is located in exon 1 (coding exon 1) of the FABP7 gene. This alteration results from a T to C substitution at nucleotide position 71, causing the leucine (L) at amino acid position 24 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

T;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Pathogenic

0.66

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.93

MutPred

0.86

Loss of stability (P = 0.0072);Loss of stability (P = 0.0072);

MVP

0.54

MPC

0.74

ClinPred

0.91

GERP RS

5.1

Varity_R

0.98

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.69

dbscSNV1_RF

Benign

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over