Genetic Variant NM_030926.6:c.152G>A (chr2-230873448-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030926.6(ITM2C):c.152G>A(p.Arg51Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000061 in 1,605,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. R51S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

ITM2C
NM_030926.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.705

Publications

2 publications found

Variant links:

Genes affected

ITM2C (HGNC:6175): (integral membrane protein 2C) Enables amyloid-beta binding activity. Involved in negative regulation of neuron projection development and neuron differentiation. Located in several cellular components, including Golgi apparatus; lysosome; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ITM2C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043691278).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030926.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITM2C	NM_030926.6	MANE Select	c.152G>A	p.Arg51Lys	missense	Exon 2 of 6	NP_112188.1	Q9NQX7-1
ITM2C	NM_001287241.2		c.152G>A	p.Arg51Lys	missense	Exon 3 of 7	NP_001274170.1	Q9NQX7-1
ITM2C	NM_001012516.2		c.152G>A	p.Arg51Lys	missense	Exon 2 of 5	NP_001012534.1	Q9NQX7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITM2C	ENST00000326427.11	TSL:1 MANE Select	c.152G>A	p.Arg51Lys	missense	Exon 2 of 6	ENSP00000322730.6	Q9NQX7-1
ITM2C	ENST00000326407.10	TSL:1	c.152G>A	p.Arg51Lys	missense	Exon 2 of 5	ENSP00000322100.6	Q9NQX7-3
ITM2C	ENST00000335005.10	TSL:1	c.121-2172G>A		intron	N/A	ENSP00000335121.6	Q9NQX7-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000492

AC:

AN:

243790

AF XY:

0.0000379

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000509

AC:

AN:

1453670

Hom.:

Cov.:

AF XY:

0.0000443

AC XY:

AN XY:

722872

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33226

American (AMR)

AF:

0.0000229

AC:

AN:

43738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.0000513

AC:

AN:

38962

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53190

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0000550

AC:

AN:

1108246

Other (OTH)

AF:

0.0000666

AC:

AN:

60094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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

AF:

0.000158

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.000434

AC:

AN:

41470

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68036

Other (OTH)

AF:

0.000478

AC:

AN:

2094

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

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000412

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.7

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.013

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.52

M_CAP

Benign

0.0046

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.095

PhyloP100

0.70

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.54

REVEL

Benign

0.022

Sift

Benign

1.0

Sift4G

Benign

0.96

Polyphen

0.0

Vest4

0.10

MutPred

0.33

Gain of ubiquitination at R51 (P = 0.009)

MVP

0.23

MPC

0.24

ClinPred

0.0061

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.051

gMVP

0.48

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over