Genetic Variant FAM78A:p.Gln117His (chr9-131261323-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001400586.1(FAM78A):c.-121G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000969 in 1,444,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

FAM78A
NM_001400586.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.207

Publications

0 publications found

Variant links:

Genes affected

FAM78A (HGNC:25465): (family with sequence similarity 78 member A)

FAM78A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.106440365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400586.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM78A	NM_033387.4	MANE Select	c.351G>T	p.Gln117His	missense	Exon 2 of 2	NP_203745.2	Q5JUQ0
FAM78A	NM_001400586.1		c.-121G>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 4	NP_001387515.1
FAM78A	NM_001400587.1		c.-121G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 3	NP_001387516.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM78A	ENST00000372271.4	TSL:1 MANE Select	c.351G>T	p.Gln117His	missense	Exon 2 of 2	ENSP00000361345.3	Q5JUQ0
FAM78A	ENST00000372269.7	TSL:1	c.342G>T	p.Gln114His	missense	Exon 4 of 4	ENSP00000361343.3	Q5JUQ2
FAM78A	ENST00000704762.1		c.351G>T	p.Gln117His	missense	Exon 3 of 3	ENSP00000516028.1	Q5JUQ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000555

AC:

AN:

234032

AF XY:

0.0000314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000387

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:

0.00

GnomAD4 exome

AF:

0.00000969

AC:

AN:

1444250

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

718554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33276

American (AMR)

AF:

0.000319

AC:

AN:

43866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25608

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

85834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108848

Other (OTH)

AF:

0.00

AC:

AN:

60030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

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:

0.0000113

ExAC

AF:

0.0000412

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

0.23

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

Eigen

Benign

-0.032

Eigen_PC

Benign

0.025

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.69

PhyloP100

0.21

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.92

REVEL

Benign

0.056

Sift

Uncertain

0.013

Sift4G

Uncertain

0.027

Polyphen

0.99

Vest4

0.11

MutPred

0.20

Gain of sheet (P = 0.1208)

MVP

0.26

MPC

1.1

ClinPred

0.12

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.071

gMVP

0.18

Mutation Taster

=81/19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over