5-151522138-C-T

Variant names:

• chr5-151522138-C-T
• rs3734050
• NM_001447.3:c.10507-52G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001447.3(FAT2):​c.10507-52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 1,410,692 control chromosomes in the GnomAD database, including 6,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (970 hom., cov: 33)
  • Exomes 𝑓: 0.091 (5636 hom.)
• Consequence: FAT2 NM_001447.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.136

Genes affected

FAT2 (HGNC:3596): (FAT atypical cadherin 2) This gene is the second identified human homolog of the Drosophila fat gene, which encodes a tumor suppressor essential for controlling cell proliferation during Drosophila development. The gene product is a member of the cadherin superfamily, a group of integral membrane proteins characterized by the presence of cadherin-type repeats. In addition to containing 34 tandem cadherin-type repeats, the gene product has two epidermal growth factor (EGF)-like repeats and one laminin G domain. This protein most likely functions as a cell adhesion molecule, controlling cell proliferation and playing an important role in cerebellum development. [provided by RefSeq, Jul 2008]

SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

MIR6499 (HGNC:49962): (microRNA 6499) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-151522138-C-T is Benign according to our data. Variant chr5-151522138-C-T is described in ClinVar as [Benign]. Clinvar id is 1277460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT2	NM_001447.3	c.10507-52G>A		intron_variant	Intron 18 of 23	ENST00000261800.6	NP_001438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT2	ENST00000261800.6	c.10507-52G>A		intron_variant	Intron 18 of 23	1	NM_001447.3	ENSP00000261800.5
FAT2	ENST00000520200.5	c.1081-52G>A		intron_variant	Intron 5 of 10	1		ENSP00000429678.1
MIR6499	ENST00000621322.1	n.11G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16324 AN: 152064 Hom.: 969 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.0551

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0994

GnomAD3 exomes AF: 0.0908 AC: 10434 AN: 114970 Hom.: 519 AF XY: 0.0885 AC XY: 5270 AN XY: 59564

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.0749

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0328

Gnomad SAS exome AF: 0.0522

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0998

Gnomad OTH exome AF: 0.0827

GnomAD4 exome AF: 0.0915 AC: 115135 AN: 1258510 Hom.: 5636 Cov.: 19 AF XY: 0.0900 AC XY: 55304 AN XY: 614748

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0717

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0797

Gnomad4 SAS exome AF: 0.0503

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0925

Gnomad4 OTH exome AF: 0.0930

GnomAD4 genome AF: 0.107 AC: 16354 AN: 152182 Hom.: 970 Cov.: 33 AF XY: 0.106 AC XY: 7897 AN XY: 74410

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0831

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0384

Gnomad4 SAS AF: 0.0558

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.0993

Alfa AF: 0.0882 Hom.: 657

Bravo AF: 0.110

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs3734050; hg19: chr5-150901699;