Variant 1-100080610-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000370152.8(MFSD14A):c.1217C>G(p.Thr406Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,613,946 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

MFSD14A
ENST00000370152.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

Variant links:

Genes affected

MFSD14A (HGNC:23363): (major facilitator superfamily domain containing 14A) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to act upstream of or within acrosome assembly; sperm mitochondrion organization; and spermatid nucleus differentiation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD14A links:

ENSG00000283761 (HGNC:):

ENSG00000283761 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20964095).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD14A	NM_033055.3 linkuse as main transcript	c.1217C>G	p.Thr406Arg	missense_variant	11/12	ENST00000370152.8	NP_149044.2	Q96MC6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD14A	ENST00000370152.8 linkuse as main transcript	c.1217C>G	p.Thr406Arg	missense_variant	11/12	1	NM_033055.3	ENSP00000359171.3		Q96MC6
ENSG00000283761	ENST00000639037.1 linkuse as main transcript	c.1886C>G	p.Thr629Arg	missense_variant	16/17	5		ENSP00000492745.1		A0A1W2PSA9

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

251404

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000199

AC:

291

AN:

1461752

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

727184

show subpopulations

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:

0.000253

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.1217C>G (p.T406R) alteration is located in exon 11 (coding exon 11) of the MFSD14A gene. This alteration results from a C to G substitution at nucleotide position 1217, causing the threonine (T) at amino acid position 406 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

0.0088

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.044

.;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.80

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

.;.;N

REVEL

Uncertain

0.33

Sift

Benign

0.54

.;.;T

Sift4G

Benign

0.50

.;.;T

Polyphen

0.0090

.;.;B

Vest4

0.54

MVP

0.26

MPC

0.99

ClinPred

0.10

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.14

gMVP

0.79

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