Variant 20-14326250-G-A details in Genebe, Genetics Data Aggregator

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

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]

FLRT3 links:

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]

MACROD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

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

Synonymous conserved (PhyloP=2 with no splicing effect.

BA1

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
FLRT3	NM_198391.3 linkuse as main transcript	c.1257C>T	p.Thr419=	synonymous_variant	3/3	ENST00000341420.5
MACROD2	NM_001351661.2 linkuse as main transcript	c.272-167229G>A		intron_variant		ENST00000684519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLRT3	ENST00000341420.5 linkuse as main transcript	c.1257C>T	p.Thr419=	synonymous_variant	3/3	2	NM_198391.3	P1
MACROD2	ENST00000684519.1 linkuse as main transcript	c.272-167229G>A		intron_variant			NM_001351661.2	P2	A1Z1Q3-1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47453

AN:

151918

Hom.:

7984

Cov.:

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.:

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

AF:

0.313

AC:

47519

AN:

152038

Hom.:

8008

Cov.:

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 submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Hypogonadotropic hypogonadism 21 with or without anosmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over