rs3734050

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001447.3. 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
	FAT2	NM_001447.3	MANE Select	c.10507-52G>A		intron	N/A	NP_001438.1	Q9NYQ8
	MIR6499	NR_106752.1		n.11G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT2	ENST00000261800.6	TSL:1 MANE Select	c.10507-52G>A		intron	N/A	ENSP00000261800.5	Q9NYQ8
	FAT2	ENST00000520200.5	TSL:1	c.1081-52G>A		intron	N/A	ENSP00000429678.1	H0YBK2
	MIR6499	ENST00000621322.1	TSL:6	n.11G>A		non_coding_transcript_exon	Exon 1 of 1

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

GnomAD2 exomes AF: 0.0908 AC: 10434 AN: 114970 AF XY: 0.0885

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 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

African (AFR) AF: 0.166 AC: 4809 AN: 29054

American (AMR) AF: 0.0717 AC: 2054 AN: 28648

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2109 AN: 19768

East Asian (EAS) AF: 0.0797 AC: 2817 AN: 35332

South Asian (SAS) AF: 0.0503 AC: 3397 AN: 67520

European-Finnish (FIN) AF: 0.100 AC: 4704 AN: 47002

Middle Eastern (MID) AF: 0.0590 AC: 212 AN: 3596

European-Non Finnish (NFE) AF: 0.0925 AC: 90162 AN: 975238

Other (OTH) AF: 0.0930 AC: 4871 AN: 52352

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

African (AFR) AF: 0.161 AC: 6689 AN: 41504

American (AMR) AF: 0.0831 AC: 1271 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3470

East Asian (EAS) AF: 0.0384 AC: 199 AN: 5180

South Asian (SAS) AF: 0.0558 AC: 269 AN: 4824

European-Finnish (FIN) AF: 0.102 AC: 1077 AN: 10578

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0907 AC: 6171 AN: 68010

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.0909 Hom.: 931

Bravo AF: 0.110

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.61
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3734050; hg19: chr5-150901699;