Variant 3-196064369-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001128148.3(TFRC):c.1258G>A(p.Gly420Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,708 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G420D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0083 ( 21 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 14 hom. )

Consequence

TFRC
NM_001128148.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

TFRC (HGNC:11763): (transferrin receptor) This gene encodes a cell surface receptor necessary for cellular iron uptake by the process of receptor-mediated endocytosis. This receptor is required for erythropoiesis and neurologic development. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]

TFRC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054885447).

BP6

Variant 3-196064369-C-T is Benign according to our data. Variant chr3-196064369-C-T is described in ClinVar as [Benign]. Clinvar id is 708777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00833 (1269/152252) while in subpopulation AFR AF= 0.0296 (1228/41536). AF 95% confidence interval is 0.0282. There are 21 homozygotes in gnomad4. There are 598 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFRC	NM_001128148.3 linkuse as main transcript	c.1258G>A	p.Gly420Ser	missense_variant	11/19	ENST00000360110.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFRC	ENST00000360110.9 linkuse as main transcript	c.1258G>A	p.Gly420Ser	missense_variant	11/19	1	NM_001128148.3	P2

Frequencies

GnomAD3 genomes

AF:

0.00834

AC:

1269

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00237

AC:

594

AN:

250990

Hom.:

AF XY:

0.00165

AC XY:

224

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.0337

Gnomad AMR exome

AF:

0.000755

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000855

AC:

1250

AN:

1461456

Hom.:

Cov.:

AF XY:

0.000736

AC XY:

535

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0322

Gnomad4 AMR exome

AF:

0.000986

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00833

AC:

1269

AN:

152252

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

598

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00954

ESP6500AA

AF:

0.0297

AC:

131

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00291

AC:

353

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.0032

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.65

T;.;T

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.84

.;N;N

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.54

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.82

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.019

.;B;B

Vest4

0.24

MVP

0.38

MPC

0.18

ClinPred

0.00083

GERP RS

-1.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.072

gMVP

0.40

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