Genetic Variant FAM219B:p.Ser21Gly (chr15-74906740-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020447.5(FAM219B):c.61A>G(p.Ser21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000084 in 1,190,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S21N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.4e-7 ( 0 hom. )

Consequence

FAM219B
NM_020447.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0317612).

BP6

Variant 15-74906740-T-C is Benign according to our data. Variant chr15-74906740-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3092308.Status of the report is criteria_provided_single_submitter, 1 stars.

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.61A>G	p.Ser21Gly	missense	Exon 1 of 5	NP_065180.1	Q5XKK7-1
FAM219B	NM_001321920.2		c.61A>G	p.Ser21Gly	missense	Exon 1 of 6	NP_001308849.1	Q5XKK7-1
FAM219B	NM_001321921.2		c.61A>G	p.Ser21Gly	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.61A>G	p.Ser21Gly	missense	Exon 1 of 5	ENSP00000350260.5	Q5XKK7-1
FAM219B	ENST00000563119.5	TSL:1	c.61A>G	p.Ser21Gly	missense	Exon 1 of 6	ENSP00000454719.1	Q5XKK7-1
FAM219B	ENST00000562698.5	TSL:1	c.61A>G	p.Ser21Gly	missense	Exon 1 of 5	ENSP00000454277.1	H3BM86

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.40e-7

AC:

AN:

1190684

Hom.:

Cov.:

AF XY:

0.00000175

AC XY:

AN XY:

572622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23748

American (AMR)

AF:

0.00

AC:

AN:

11114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16042

East Asian (EAS)

AF:

0.0000360

AC:

AN:

27794

South Asian (SAS)

AF:

0.00

AC:

AN:

43236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3918

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

976826

Other (OTH)

AF:

0.00

AC:

AN:

48204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.050

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.1

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.0026

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.51

M_CAP

Benign

0.0063

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.13

PhyloP100

-0.020

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.32

REVEL

Benign

0.012

Sift

Benign

0.86

Sift4G

Benign

0.60

Polyphen

0.0

Vest4

0.071

MutPred

0.12

Loss of phosphorylation at S21 (P = 0.001)

MVP

0.030

MPC

0.25

ClinPred

0.048

GERP RS

-2.8

PromoterAI

-0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.034

gMVP

0.12

Mutation Taster

=98/2

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