Genetic Variant NM_014077.4:c.138G>C (chr19-16185687-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014077.4(FAM32A):c.138G>C(p.Lys46Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000012 in 1,578,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FAM32A
NM_014077.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

Publications

3 publications found

Variant links:

Genes affected

FAM32A (HGNC:24563): (family with sequence similarity 32 member A) Enables RNA binding activity. Predicted to be involved in apoptotic process. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM32A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.122205675).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014077.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM32A	NM_014077.4	MANE Select	c.138G>C	p.Lys46Asn	missense	Exon 2 of 4	NP_054796.1	Q9Y421-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM32A	ENST00000263384.12	TSL:1 MANE Select	c.138G>C	p.Lys46Asn	missense	Exon 2 of 4	ENSP00000263384.6	Q9Y421-1
FAM32A	ENST00000589852.5	TSL:1	c.78G>C	p.Lys26Asn	missense	Exon 1 of 3	ENSP00000465969.1	Q9Y421-3
FAM32A	ENST00000921004.1		c.138G>C	p.Lys46Asn	missense	Exon 2 of 4	ENSP00000591063.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000262

AC:

AN:

191096

AF XY:

0.0000295

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:

0.0000623

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1425654

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

705278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32944

American (AMR)

AF:

0.00

AC:

AN:

38692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25506

East Asian (EAS)

AF:

0.00

AC:

AN:

38664

South Asian (SAS)

AF:

0.00

AC:

AN:

81534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

1092612

Other (OTH)

AF:

0.00

AC:

AN:

59140

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:

0.0000197

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41594

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000282

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000336

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.67

M_CAP

Benign

0.0052

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

PhyloP100

4.4

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.86

REVEL

Benign

0.095

Sift

Benign

0.39

Sift4G

Benign

0.23

Polyphen

0.99

Vest4

0.23

MutPred

0.43

Loss of ubiquitination at K46 (P = 0.0059)

MVP

0.19

MPC

1.2

ClinPred

0.71

GERP RS

2.5

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.22

Mutation Taster

=79/21

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

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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