rs568406248

Variant names:

• chr15-74902675-T-C
• rs568406248
• NM_020447.5:c.541A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_020447.5(FAM219B):​c.541A>G​(p.Thr181Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,613,270 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (1 hom.)
• Consequence: FAM219B NM_020447.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011962891).
• BP6: Variant 15-74902675-T-C is Benign according to our data. Variant chr15-74902675-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2226630.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM219B	NM_020447.5	MANE Select	c.541A>G	p.Thr181Ala	missense	Exon 5 of 5	NP_065180.1	Q5XKK7-1
	FAM219B	NM_001321920.2		c.541A>G	p.Thr181Ala	missense	Exon 5 of 6	NP_001308849.1	Q5XKK7-1
	FAM219B	NM_001321921.2		c.541A>G	p.Thr181Ala	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.541A>G	p.Thr181Ala	missense	Exon 5 of 5	ENSP00000350260.5	Q5XKK7-1
	FAM219B	ENST00000563119.5	TSL:1	c.541A>G	p.Thr181Ala	missense	Exon 5 of 6	ENSP00000454719.1	Q5XKK7-1
	FAM219B	ENST00000565772.5	TSL:1	c.283A>G	p.Thr95Ala	missense	Exon 4 of 4	ENSP00000455248.1	H3BPC2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000917 AC: 23 AN: 250744 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000568 AC: 83 AN: 1460994 Hom.: 1 Cov.: 31 AF XY: 0.0000812 AC XY: 59 AN XY: 726754

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.000617 AC: 53 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111606

Other (OTH) AF: 0.0000331 AC: 2 AN: 60364

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000936 Hom.: 1

Bravo AF: 0.0000113

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.059
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.042
DANN	Benign	0.40
DEOGEN2	Benign	0.020	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.2
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.062
Sift	Benign	0.27	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.026
MutPred		0.16		Loss of helix (P = 0.0123)
MVP		0.030
MPC		0.27
ClinPred		0.035	T
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.068
Mutation Taster		=94/6	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: rs568406248; hg19: chr15-75195016;