chr8-12185382-C-T

Variant names:

• chr8-12185382-C-T
• rs779452363
• NM_001083537.4:c.784G>A

Variant summary

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

The NM_001083537.4(FAM86B1):​c.784G>A​(p.Glu262Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000031 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.788
• Publications: 2 publications found

Genes affected

FAM86B1 (HGNC:28268): (family with sequence similarity 86 member B1) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. [provided by Alliance of Genome Resources, Apr 2022]

FAM66D (HGNC:24159): (family with sequence similarity 66 member D)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083537.4. 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
	FAM86B1	NM_001083537.4	MANE Select	c.784G>A	p.Glu262Lys	missense	Exon 6 of 7	NP_001077006.1	Q8N7N1-2
	FAM86B1	NR_003494.3		n.581G>A		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM86B1	ENST00000448228.7	TSL:5 MANE Select	c.784G>A	p.Glu262Lys	missense	Exon 6 of 7	ENSP00000407067.2	Q8N7N1-2
	FAM86B1	ENST00000524893.5	TSL:1	n.*334G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000436024.1	E9PLW5
	FAM86B1	ENST00000524893.5	TSL:1	n.*334G>A		3_prime_UTR	Exon 4 of 5	ENSP00000436024.1	E9PLW5

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148564 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000246

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000377 AC: 9 AN: 238698 AF XY: 0.0000462

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000303

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000584

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.000169

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000306 AC: 44 AN: 1439532 Hom.: 3 Cov.: 94 AF XY: 0.0000349 AC XY: 25 AN XY: 715904

⚠️ 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: 33226

American (AMR) AF: 0.0000230 AC: 1 AN: 43424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.0000786 AC: 3 AN: 38178

South Asian (SAS) AF: 0.0000359 AC: 3 AN: 83478

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52226

Middle Eastern (MID) AF: 0.000390 AC: 2 AN: 5134

European-Non Finnish (NFE) AF: 0.0000291 AC: 32 AN: 1098558

Other (OTH) AF: 0.0000336 AC: 2 AN: 59462

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000135 AC: 2 AN: 148564 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 1 AN XY: 72406

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

African (AFR) AF: 0.0000246 AC: 1 AN: 40624

American (AMR) AF: 0.00 AC: 0 AN: 14654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 4840

South Asian (SAS) AF: 0.00 AC: 0 AN: 4526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66824

Other (OTH) AF: 0.00 AC: 0 AN: 2024

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000966 Hom.: 1

ExAC AF: 0.0000256 AC: 3

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	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0038	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.79
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.12
Sift	Benign	0.19	T
Sift4G	Benign	0.32	T
Polyphen		0.0020	B
Vest4		0.47
MutPred		0.57		Gain of ubiquitination at E296 (P = 0.0325)
MVP		0.068
MPC		2.0
ClinPred		0.051	T
GERP RS		1.2
Varity_R		0.052
gMVP		0.46
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs779452363; hg19: chr8-12042891; COSMIC: COSV58668000; COSMIC: COSV58668000;