Genetic Variant NM_013280.5:c.64G>C (chr11-64116331-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013280.5(FLRT1):c.64G>C(p.Val22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V22I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FLRT1
NM_013280.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

0 publications found

Variant links:

Genes affected

FLRT1 (HGNC:3760): (fibronectin leucine rich transmembrane protein 1) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. The family members may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. The encoded protein shares sequence similarity with two other family members, FLRT2 and FLRT3. This gene is expressed in kidney and brain. [provided by RefSeq, Jul 2008]

FLRT1 links:

MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MACROD1 links:

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ACMG classification

Classification was made for transcript

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=0.1673024).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013280.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLRT1	NM_013280.5	MANE Select	c.64G>C	p.Val22Leu	missense	Exon 3 of 3	NP_037412.2
MACROD1	NM_014067.4	MANE Select	c.517+34908C>G		intron	N/A	NP_054786.2
FLRT1	NM_001384466.1		c.64G>C	p.Val22Leu	missense	Exon 3 of 3	NP_001371395.1	Q9NZU1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLRT1	ENST00000682287.1	MANE Select	c.64G>C	p.Val22Leu	missense	Exon 3 of 3	ENSP00000507207.1	Q9NZU1-2
FLRT1	ENST00000246841.3	TSL:1	c.64G>C	p.Val22Leu	missense	Exon 2 of 2	ENSP00000246841.3	Q9NZU1-2
MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+34908C>G		intron	N/A	ENSP00000255681.6	Q9BQ69

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458580

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

85898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111078

Other (OTH)

AF:

0.00

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.8

(source)

DANN

Benign

0.91

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.029

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

PhyloP100

1.5

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.20

REVEL

Benign

0.026

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.043

Vest4

0.21

MutPred

0.41

Loss of sheet (P = 0.007)

MVP

0.47

MPC

0.29

ClinPred

0.73

GERP RS

1.9

gMVP

0.46

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over