Genetic Variant NM_020447.5:c.55C>G (chr15-74906746-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_020447.5(FAM219B):c.55C>G(p.Arg19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. R19W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM219B
NM_020447.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.640

Publications

0 publications found

Variant links:

Genes affected

FAM219B (HGNC:24695): (family with sequence similarity 219 member B)

FAM219B 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=0.0965918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020447.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM219B	NM_020447.5	MANE Select	c.55C>G	p.Arg19Gly	missense	Exon 1 of 5	NP_065180.1	Q5XKK7-1
FAM219B	NM_001321920.2		c.55C>G	p.Arg19Gly	missense	Exon 1 of 6	NP_001308849.1	Q5XKK7-1
FAM219B	NM_001321921.2		c.55C>G	p.Arg19Gly	missense	Exon 1 of 6	NP_001308850.1	Q5XKK7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM219B	ENST00000357635.10	TSL:1 MANE Select	c.55C>G	p.Arg19Gly	missense	Exon 1 of 5	ENSP00000350260.5	Q5XKK7-1
FAM219B	ENST00000563119.5	TSL:1	c.55C>G	p.Arg19Gly	missense	Exon 1 of 6	ENSP00000454719.1	Q5XKK7-1
FAM219B	ENST00000562698.5	TSL:1	c.55C>G	p.Arg19Gly	missense	Exon 1 of 5	ENSP00000454277.1	H3BM86

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1173494

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

562528

African (AFR)

AF:

0.00

AC:

AN:

23532

American (AMR)

AF:

0.00

AC:

AN:

10004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15772

East Asian (EAS)

AF:

0.00

AC:

AN:

27368

South Asian (SAS)

AF:

0.00

AC:

AN:

39478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

967922

Other (OTH)

AF:

0.00

AC:

AN:

47492

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.023

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.66

M_CAP

Benign

0.037

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.64

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.3

REVEL

Benign

0.038

Sift

Uncertain

0.0050

Sift4G

Benign

0.091

Polyphen

0.0

Vest4

0.098

MutPred

0.26

Loss of MoRF binding (P = 0.007)

MVP

0.055

MPC

0.36

ClinPred

0.14

GERP RS

0.66

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.093

gMVP

0.36

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