Genetic Variant NM_138373.5:c.742G>C (chr19-53874271-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138373.5(MYADM):c.742G>C(p.Val248Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,457,236 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V248I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MYADM
NM_138373.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.56

Publications

0 publications found

Variant links:

Genes affected

MYADM (HGNC:7544): (myeloid associated differentiation marker) Involved in several processes, including negative regulation of heterotypic cell-cell adhesion; negative regulation of macromolecule metabolic process; and negative regulation of protein kinase C signaling. Located in several cellular components, including cortical actin cytoskeleton; membrane raft; and ruffle. [provided by Alliance of Genome Resources, Apr 2022]

MYADM links:

MYADM-AS2 (HGNC:40385): (MYADM antisense RNA 2)

MYADM-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138373.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYADM	NM_138373.5	MANE Select	c.742G>C	p.Val248Leu	missense	Exon 3 of 3	NP_612382.1	Q96S97
MYADM	NM_001020818.2		c.742G>C	p.Val248Leu	missense	Exon 2 of 2	NP_001018654.1	Q96S97
MYADM	NM_001020819.3		c.742G>C	p.Val248Leu	missense	Exon 3 of 3	NP_001018655.1	Q96S97

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYADM	ENST00000391770.9	TSL:1 MANE Select	c.742G>C	p.Val248Leu	missense	Exon 3 of 3	ENSP00000375650.4	Q96S97
MYADM	ENST00000391768.2	TSL:1	c.742G>C	p.Val248Leu	missense	Exon 2 of 2	ENSP00000375648.2	Q96S97
MYADM	ENST00000391769.3	TSL:1	c.742G>C	p.Val248Leu	missense	Exon 3 of 3	ENSP00000375649.2	Q96S97

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248606

AF XY:

0.00000745

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1457236

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25844

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

85870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1108766

Other (OTH)

AF:

0.00

AC:

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.4

PhyloP100

4.6

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.32

Sift

Benign

0.041

Sift4G

Benign

0.062

Polyphen

1.0

Vest4

0.26

MutPred

0.59

Loss of catalytic residue at V248 (P = 0.0473)

MVP

0.22

MPC

1.0

ClinPred

0.83

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.14

gMVP

0.82

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over