chr8-12428653-G-A

Variant names:

• chr8-12428653-G-A
• rs1443678382
• NM_001137610.3:c.722C>T

Variant summary

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

The NM_001137610.3(FAM86B2):​c.722C>T​(p.Pro241Leu) variant causes a missense change. 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. P241T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000055 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0000083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.24
• Publications: 0 publications found

Genes affected

FAM86B2 (HGNC:32222): (family with sequence similarity 86 member B2) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

FAM66A (HGNC:30444): (family with sequence similarity 66 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137610.3. 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
	FAM86B2	NM_001137610.3	MANE Select	c.722C>T	p.Pro241Leu	missense	Exon 6 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.431+328C>T		intron	N/A
	FAM86B2	NR_148877.2		n.350+328C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM86B2	ENST00000262365.9	TSL:5 MANE Select	c.722C>T	p.Pro241Leu	missense	Exon 6 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.692C>T	p.Pro231Leu	missense	Exon 6 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.620C>T	p.Pro207Leu	missense	Exon 5 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes AF: 0.0000549 AC: 8 AN: 145672 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000508

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000139

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: 0.0000603

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000100 AC: 1 AN: 99970 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: 0.0000234

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000828 AC: 11 AN: 1328872 Hom.: 0 Cov.: 31 AF XY: 0.00000915 AC XY: 6 AN XY: 655654

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28902

American (AMR) AF: 0.00 AC: 0 AN: 32690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22246

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 72896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3802

European-Non Finnish (NFE) AF: 0.00000863 AC: 9 AN: 1042788

Other (OTH) AF: 0.0000360 AC: 2 AN: 55610

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000368995), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000549 AC: 8 AN: 145672 Hom.: 0 Cov.: 24 AF XY: 0.0000565 AC XY: 4 AN XY: 70752

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000508 AC: 2 AN: 39370

American (AMR) AF: 0.000139 AC: 2 AN: 14398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.00 AC: 0 AN: 4624

South Asian (SAS) AF: 0.00 AC: 0 AN: 4324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000603 AC: 4 AN: 66284

Other (OTH) AF: 0.00 AC: 0 AN: 1962

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000000669465), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0055	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.12
Sift	Benign	0.088	T
Sift4G	Benign	0.33	T
Polyphen		0.097	B
Vest4		0.39
MutPred		0.70		Loss of sheet (P = 0.1501)
MVP		0.082
MPC		1.9
ClinPred		0.37	T
GERP RS		1.2
Varity_R		0.097
gMVP		0.51
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1443678382; hg19: chr8-12286162;