chr20-14325865-C-G

Position:

• chr20-14325865-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198391.3(FLRT3):​c.1642G>C​(p.Val548Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FLRT3 NM_198391.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.05

Genes affected

FLRT3 (HGNC:3762): (fibronectin leucine rich transmembrane protein 3) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. FLRTs may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. This gene is expressed in many tissues. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2010]

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLRT3	NM_198391.3	c.1642G>C	p.Val548Leu	missense_variant	3/3	ENST00000341420.5	NP_938205.1
MACROD2	NM_001351661.2	c.272-167614C>G		intron_variant		ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLRT3	ENST00000341420.5	c.1642G>C	p.Val548Leu	missense_variant	3/3	2	NM_198391.3	ENSP00000339912	P1
MACROD2	ENST00000684519.1	c.272-167614C>G		intron_variant			NM_001351661.2	ENSP00000507484	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727146

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

High myopia Uncertain:1

Uncertain significance, no assertion criteria provided

research

Institute of Human Genetics, Polish Academy of Sciences

Dec 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.064	T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.20
Sift	Benign	0.15	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.15	B;B
Vest4		0.63
MutPred		0.40		Loss of MoRF binding (P = 0.1764);Loss of MoRF binding (P = 0.1764);
MVP		0.54
MPC		0.53
ClinPred		0.75	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs1345083050; hg19: chr20-14306511;