Genetic Variant NM_018691.4:c.1489C>T (chr5-153993005-G-A) – 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_018691.4(FAM114A2):c.1489C>T(p.Gln497*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000124 in 1,611,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FAM114A2
NM_018691.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.07

Publications

1 publications found

Variant links:

Genes affected

FAM114A2 (HGNC:1333): (family with sequence similarity 114 member A2)

FAM114A2 links:

Genome browser will be placed here

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_018691.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM114A2	NM_018691.4	MANE Select	c.1489C>T	p.Gln497*	stop_gained	Exon 14 of 14	NP_061161.2	A0A140VKG4
FAM114A2	NM_001317993.2		c.1489C>T	p.Gln497*	stop_gained	Exon 15 of 15	NP_001304922.1	Q9NRY5
FAM114A2	NM_001317994.2		c.1489C>T	p.Gln497*	stop_gained	Exon 14 of 14	NP_001304923.1	A0A140VKG4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM114A2	ENST00000351797.9	TSL:1 MANE Select	c.1489C>T	p.Gln497*	stop_gained	Exon 14 of 14	ENSP00000341597.4	Q9NRY5
FAM114A2	ENST00000520667.5	TSL:1	c.1489C>T	p.Gln497*	stop_gained	Exon 15 of 15	ENSP00000430384.1	Q9NRY5
FAM114A2	ENST00000522858.5	TSL:1	c.1489C>T	p.Gln497*	stop_gained	Exon 14 of 14	ENSP00000430489.1	Q9NRY5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250294

AF XY:

0.00000739

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459436

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

85924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110496

Other (OTH)

AF:

0.00

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.84

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.78

PhyloP100

4.1

Vest4

0.11

GERP RS

5.5

Mutation Taster

=81/119

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over