dbSNP rs761537555: FAM193A:p.Glu633Lys (chr4-2662989-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001366318.2(FAM193A):c.1897G>A(p.Glu633Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000274 in 1,459,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FAM193A
NM_001366318.2 missense, splice_region

Scores

Splicing: ADA: 0.9596

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

Publications

0 publications found

Variant links:

Genes affected

FAM193A (HGNC:16822): (family with sequence similarity 193 member A)

FAM193A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366318.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM193A	NM_001366318.2	MANE Select	c.1897G>A	p.Glu633Lys	missense splice_region	Exon 11 of 21	NP_001353247.1	A0A1B0GVL4
FAM193A	NM_001366316.2		c.1726G>A	p.Glu576Lys	missense splice_region	Exon 11 of 21	NP_001353245.1
FAM193A	NM_001256666.2		c.1024G>A	p.Glu342Lys	missense splice_region	Exon 9 of 20	NP_001243595.1	P78312-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM193A	ENST00000637812.2	TSL:5 MANE Select	c.1897G>A	p.Glu633Lys	missense splice_region	Exon 11 of 21	ENSP00000490564.1	A0A1B0GVL4
FAM193A	ENST00000324666.9	TSL:1	c.1024G>A	p.Glu342Lys	missense splice_region	Exon 9 of 20	ENSP00000324587.5	P78312-1
FAM193A	ENST00000502458.5	TSL:1	c.1090G>A	p.Glu364Lys	missense splice_region	Exon 10 of 20	ENSP00000427505.1	P78312-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251402

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459786

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.0000671

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.00

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110212

Other (OTH)

AF:

0.0000166

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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

0.24

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0059

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.012

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

5.9

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.68

REVEL

Benign

0.097

Sift

Benign

0.12

Sift4G

Benign

0.43

Polyphen

0.35

Vest4

0.34

MutPred

0.15

Gain of ubiquitination at E342 (P = 0)

MVP

0.043

MPC

0.72

ClinPred

0.47

GERP RS

5.9

Varity_R

0.093

gMVP

0.31

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.96

dbscSNV1_RF

Pathogenic

0.73

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