dbSNP rs779785935: FAM53A:p.Val382Phe (chr4-1641346-C-A) – 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_001174070.3(FAM53A):c.1144G>T(p.Val382Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,782 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. V382I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FAM53A
NM_001174070.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

Publications

0 publications found

Variant links:

Genes affected

FAM53A (HGNC:31860): (family with sequence similarity 53 member A) Predicted to be involved in protein import into nucleus. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM53A 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=0.08075121).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174070.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM53A	NM_001174070.3	MANE Select	c.1144G>T	p.Val382Phe	missense	Exon 5 of 5	NP_001167541.1	Q6NSI3
FAM53A	NM_001013622.3		c.1144G>T	p.Val382Phe	missense	Exon 5 of 5	NP_001013644.1	Q6NSI3
FAM53A	NM_001297435.1		c.*215G>T		3_prime_UTR	Exon 6 of 6	NP_001284364.1	C9JYQ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM53A	ENST00000308132.11	TSL:2 MANE Select	c.1144G>T	p.Val382Phe	missense	Exon 5 of 5	ENSP00000310057.6	Q6NSI3
FAM53A	ENST00000472884.6	TSL:1	c.1144G>T	p.Val382Phe	missense	Exon 5 of 5	ENSP00000426260.1	Q6NSI3
FAM53A	ENST00000461064.5	TSL:2	c.1144G>T	p.Val382Phe	missense	Exon 4 of 4	ENSP00000418243.1	Q6NSI3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

43600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25986

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

85980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111254

Other (OTH)

AF:

0.00

AC:

AN:

60248

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.087

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.012

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.49

M_CAP

Benign

0.018

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

PhyloP100

-1.5

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

REVEL

Benign

0.069

Sift

Benign

0.040

Sift4G

Benign

0.15

Polyphen

0.77

Vest4

0.16

MutPred

0.25

Loss of sheet (P = 0.1907)

MVP

0.048

MPC

0.12

ClinPred

0.18

GERP RS

-4.9

Varity_R

0.083

gMVP

0.14

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over