chr8-12185382-C-A

Variant names:

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

Variant summary

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

The NM_001083537.4(FAM86B1):​c.784G>T​(p.Glu262*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Glu262*	stop_gained	Exon 6 of 7	NP_001077006.1	Q8N7N1-2
	FAM86B1	NR_003494.3		n.581G>T		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>T	p.Glu262*	stop_gained	Exon 6 of 7	ENSP00000407067.2	Q8N7N1-2
	FAM86B1	ENST00000524893.5	TSL:1	n.*334G>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000436024.1	E9PLW5
	FAM86B1	ENST00000524893.5	TSL:1	n.*334G>T		3_prime_UTR	Exon 4 of 5	ENSP00000436024.1	E9PLW5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000419 AC: 1 AN: 238698 AF XY: 0.00

Gnomad AFR exome AF: 0.0000699

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: 0.00000278 AC: 4 AN: 1439560 Hom.: 0 Cov.: 94 AF XY: 0.00000140 AC XY: 1 AN XY: 715918

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

African (AFR) AF: 0.0000301 AC: 1 AN: 33226

American (AMR) AF: 0.00 AC: 0 AN: 43426

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 38178

South Asian (SAS) AF: 0.00 AC: 0 AN: 83482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52226

Middle Eastern (MID) AF: 0.000195 AC: 1 AN: 5136

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1098574

Other (OTH) AF: 0.00 AC: 0 AN: 59466

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0126737), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Benign	0.18
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.34	N
PhyloP100		0.79
Vest4		0.081
GERP RS		1.2
Mutation Taster		=91/109	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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;