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GeneBe

20-14326250-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198391.3(FLRT3):c.1257C>T(p.Thr419=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,613,644 control chromosomes in the GnomAD database, including 62,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8008 hom., cov: 32)
Exomes 𝑓: 0.27 ( 54720 hom. )

Consequence

FLRT3
NM_198391.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.00
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-14326250-G-A is Benign according to our data. Variant chr20-14326250-G-A is described in ClinVar as [Benign]. Clinvar id is 1226971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FLRT3NM_198391.3 linkuse as main transcriptc.1257C>T p.Thr419= synonymous_variant 3/3 ENST00000341420.5
MACROD2NM_001351661.2 linkuse as main transcriptc.272-167229G>A intron_variant ENST00000684519.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FLRT3ENST00000341420.5 linkuse as main transcriptc.1257C>T p.Thr419= synonymous_variant 3/32 NM_198391.3 P1
MACROD2ENST00000684519.1 linkuse as main transcriptc.272-167229G>A intron_variant NM_001351661.2 P2A1Z1Q3-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.312
AC:
47453
AN:
151918
Hom.:
7984
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.430
Gnomad AMI
AF:
0.369
Gnomad AMR
AF:
0.221
Gnomad ASJ
AF:
0.242
Gnomad EAS
AF:
0.370
Gnomad SAS
AF:
0.345
Gnomad FIN
AF:
0.288
Gnomad MID
AF:
0.324
Gnomad NFE
AF:
0.261
Gnomad OTH
AF:
0.302
GnomAD3 exomes
AF:
0.274
AC:
68619
AN:
250428
Hom.:
10179
AF XY:
0.276
AC XY:
37323
AN XY:
135306
show subpopulations
Gnomad AFR exome
AF:
0.433
Gnomad AMR exome
AF:
0.149
Gnomad ASJ exome
AF:
0.260
Gnomad EAS exome
AF:
0.373
Gnomad SAS exome
AF:
0.319
Gnomad FIN exome
AF:
0.273
Gnomad NFE exome
AF:
0.262
Gnomad OTH exome
AF:
0.284
GnomAD4 exome
AF:
0.269
AC:
392958
AN:
1461606
Hom.:
54720
Cov.:
37
AF XY:
0.271
AC XY:
196813
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.436
Gnomad4 AMR exome
AF:
0.157
Gnomad4 ASJ exome
AF:
0.258
Gnomad4 EAS exome
AF:
0.316
Gnomad4 SAS exome
AF:
0.319
Gnomad4 FIN exome
AF:
0.272
Gnomad4 NFE exome
AF:
0.261
Gnomad4 OTH exome
AF:
0.288
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.313
AC:
47519
AN:
152038
Hom.:
8008
Cov.:
32
AF XY:
0.312
AC XY:
23185
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.431
Gnomad4 AMR
AF:
0.220
Gnomad4 ASJ
AF:
0.242
Gnomad4 EAS
AF:
0.369
Gnomad4 SAS
AF:
0.344
Gnomad4 FIN
AF:
0.288
Gnomad4 NFE
AF:
0.261
Gnomad4 OTH
AF:
0.307
Alfa
AF:
0.271
Hom.:
7733
Bravo
AF:
0.311
Asia WGS
AF:
0.363
AC:
1259
AN:
3478
EpiCase
AF:
0.275
EpiControl
AF:
0.265

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 11, 2018- -
Hypogonadotropic hypogonadism 21 with or without anosmia Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
6.2
Dann
Benign
0.78

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

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

Other links and lift over

dbSNP: rs6042672; hg19: chr20-14306896; COSMIC: COSV53996346; COSMIC: COSV53996346; API