Variant 19-4670295-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019107.4(MYDGF):c.40A>T(p.Ser14Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,510,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

MYDGF
NM_019107.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.277

Variant links:

Genes affected

MYDGF (HGNC:16948): (myeloid derived growth factor) The protein encoded by this gene was previously thought to support proliferation of lymphoid cells and was considered an interleukin. However, this activity has not been reproducible and the function of this protein is currently unknown. [provided by RefSeq, Jul 2008]

MYDGF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018522173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYDGF	NM_019107.4 linkuse as main transcript	c.40A>T	p.Ser14Cys	missense_variant	1/6	ENST00000262947.8	NP_061980.1	Q969H8
MYDGF	XM_017026987.2 linkuse as main transcript	c.40A>T	p.Ser14Cys	missense_variant	1/4		XP_016882476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYDGF	ENST00000262947.8 linkuse as main transcript	c.40A>T	p.Ser14Cys	missense_variant	1/6	1	NM_019107.4	ENSP00000262947.2		Q969H8
MYDGF	ENST00000599630.1 linkuse as main transcript	c.40A>T	p.Ser14Cys	missense_variant	1/5	2		ENSP00000469945.1		M0QYN0

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000476

AC:

AN:

105108

Hom.:

AF XY:

0.0000167

AC XY:

AN XY:

59760

show subpopulations

Gnomad AFR exome

AF:

0.00143

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:

0.00

Gnomad OTH exome

AF:

0.000381

GnomAD4 exome

AF:

0.0000250

AC:

AN:

1358024

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

670088

show subpopulations

Gnomad4 AFR exome

AF:

0.000925

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:

0.00

Gnomad4 OTH exome

AF:

0.000125

GnomAD4 genome

AF:

0.000250

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000235

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.00101

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000197

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3470

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

Sep 15, 2021

The c.40A>T (p.S14C) alteration is located in exon 1 (coding exon 1) of the MYDGF gene. This alteration results from a A to T substitution at nucleotide position 40, causing the serine (S) at amino acid position 14 to be replaced by a cysteine (C). 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

0.074

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.0

DANN

Benign

0.78

DEOGEN2

Benign

0.081

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.99

PROVEAN

Benign

-0.53

N;.

REVEL

Benign

0.017

Sift

Benign

0.10

T;.

Sift4G

Benign

0.085

T;T

Polyphen

0.33

B;.

Vest4

0.24

MVP

0.014

MPC

0.68

ClinPred

0.020

GERP RS

0.68

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.080

gMVP

0.27

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