rs1442147612

Variant names:

• chr15-74906746-G-A
• rs1442147612
• NM_020447.5:c.55C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-74906746-G-A
• chr15-74906746-G-C
• chr15-74906746-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020447.5(FAM219B):​c.55C>T​(p.Arg19Trp) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM219B NM_020447.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.640
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12080222).

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.55C>T	p.Arg19Trp	missense	Exon 1 of 5	NP_065180.1	Q5XKK7-1
	FAM219B	NM_001321920.2		c.55C>T	p.Arg19Trp	missense	Exon 1 of 6	NP_001308849.1	Q5XKK7-1
	FAM219B	NM_001321921.2		c.55C>T	p.Arg19Trp	missense	Exon 1 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.55C>T	p.Arg19Trp	missense	Exon 1 of 5	ENSP00000350260.5	Q5XKK7-1
	FAM219B	ENST00000563119.5	TSL:1	c.55C>T	p.Arg19Trp	missense	Exon 1 of 6	ENSP00000454719.1	Q5XKK7-1
	FAM219B	ENST00000562698.5	TSL:1	c.55C>T	p.Arg19Trp	missense	Exon 1 of 5	ENSP00000454277.1	H3BM86

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 14506 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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 Data not reliable, filtered out with message: AS_VQSR AF: 8.52e-7 AC: 1 AN: 1173494 Hom.: 0 Cov.: 30 AF XY: 0.00000178 AC XY: 1 AN XY: 562528

African (AFR) AF: 0.00 AC: 0 AN: 23532

American (AMR) AF: 0.00 AC: 0 AN: 10004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15772

East Asian (EAS) AF: 0.00 AC: 0 AN: 27368

South Asian (SAS) AF: 0.00 AC: 0 AN: 39478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3746

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 967922

Other (OTH) AF: 0.00 AC: 0 AN: 47492

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

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	Benign	0.097
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.64
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.030
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.19		Loss of methylation at R19 (P = 0.0328)
MVP		0.055
MPC		0.77
ClinPred		0.62	D
GERP RS		0.66
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.080
gMVP		0.32

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

Other links and lift over

dbSNP: rs1442147612; hg19: chr15-75199087;