chr15-74906786-C-A

Variant names:

• chr15-74906786-C-A
• rs1416706695
• NM_020447.5:c.15G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020447.5(FAM219B):​c.15G>T​(p.Glu5Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000855 in 1,287,108 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E5G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000088 (0 hom.)
• Consequence: FAM219B NM_020447.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.293
• Publications: 0 publications found

Genes affected

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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05879715).

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.15G>T	p.Glu5Asp	missense	Exon 1 of 5	NP_065180.1	Q5XKK7-1
	FAM219B	NM_001321920.2		c.15G>T	p.Glu5Asp	missense	Exon 1 of 6	NP_001308849.1	Q5XKK7-1
	FAM219B	NM_001321921.2		c.15G>T	p.Glu5Asp	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.15G>T	p.Glu5Asp	missense	Exon 1 of 5	ENSP00000350260.5	Q5XKK7-1
	FAM219B	ENST00000563119.5	TSL:1	c.15G>T	p.Glu5Asp	missense	Exon 1 of 6	ENSP00000454719.1	Q5XKK7-1
	FAM219B	ENST00000562698.5	TSL:1	c.15G>T	p.Glu5Asp	missense	Exon 1 of 5	ENSP00000454277.1	H3BM86

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000881 AC: 10 AN: 1134892 Hom.: 0 Cov.: 30 AF XY: 0.00000555 AC XY: 3 AN XY: 540208

African (AFR) AF: 0.00 AC: 0 AN: 23066

American (AMR) AF: 0.00 AC: 0 AN: 8738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15222

East Asian (EAS) AF: 0.00 AC: 0 AN: 26674

South Asian (SAS) AF: 0.00 AC: 0 AN: 31444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3166

European-Non Finnish (NFE) AF: 0.0000105 AC: 10 AN: 949972

Other (OTH) AF: 0.00 AC: 0 AN: 46138

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.7
DANN	Benign	0.93
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.29
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.018
Sift	Benign	0.29	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.059
MutPred		0.21		Gain of MoRF binding (P = 0.1157)
MVP		0.030
MPC		0.25
ClinPred		0.066	T
GERP RS		0.76
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.055
gMVP		0.20
Mutation Taster		=97/3	polymorphism

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: rs1416706695; hg19: chr15-75199127;