NM_020447.5:c.524A>C

Variant names:

• chr15-74902692-T-G
• NM_020447.5:c.524A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020447.5(FAM219B):​c.524A>C​(p.Lys175Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM219B NM_020447.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.07
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM219B	NM_020447.5	MANE Select	c.524A>C	p.Lys175Thr	missense	Exon 5 of 5	NP_065180.1	Q5XKK7-1
	FAM219B	NM_001321920.2		c.524A>C	p.Lys175Thr	missense	Exon 5 of 6	NP_001308849.1	Q5XKK7-1
	FAM219B	NM_001321921.2		c.524A>C	p.Lys175Thr	missense	Exon 5 of 6	NP_001308850.1	Q5XKK7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM219B	ENST00000357635.10	TSL:1 MANE Select	c.524A>C	p.Lys175Thr	missense	Exon 5 of 5	ENSP00000350260.5	Q5XKK7-1
	FAM219B	ENST00000563119.5	TSL:1	c.524A>C	p.Lys175Thr	missense	Exon 5 of 6	ENSP00000454719.1	Q5XKK7-1
	FAM219B	ENST00000565772.5	TSL:1	c.266A>C	p.Lys89Thr	missense	Exon 4 of 4	ENSP00000455248.1	H3BPC2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.24		Loss of ubiquitination at K175 (P = 0.0039)
MVP		0.20
MPC		1.1
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.24
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr15-75195033;