8-12185402-G-A

Variant names:

• chr8-12185402-G-A
• rs775301778
• NM_001083537.4:c.764C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001083537.4(FAM86B1):​c.764C>T​(p.Thr255Met) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000048 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38
• Publications: 4 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3813037).

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.764C>T	p.Thr255Met	missense	Exon 6 of 7	NP_001077006.1	Q8N7N1-2
	FAM86B1	NR_003494.3		n.561C>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.764C>T	p.Thr255Met	missense	Exon 6 of 7	ENSP00000407067.2	Q8N7N1-2
	FAM86B1	ENST00000524893.5	TSL:1	n.*314C>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000436024.1	E9PLW5
	FAM86B1	ENST00000524893.5	TSL:1	n.*314C>T		3_prime_UTR	Exon 4 of 5	ENSP00000436024.1	E9PLW5

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 15 AN: 148520 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000207

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000210

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000933 AC: 22 AN: 235918 AF XY: 0.0000700

Gnomad AFR exome AF: 0.0000704

Gnomad AMR exome AF: 0.0000939

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000659

Gnomad FIN exome AF: 0.000145

Gnomad NFE exome AF: 0.0000278

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000479 AC: 69 AN: 1440168 Hom.: 5 Cov.: 94 AF XY: 0.0000419 AC XY: 30 AN XY: 716206

⚠️ 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: 33240

American (AMR) AF: 0.0000921 AC: 4 AN: 43432

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25856

East Asian (EAS) AF: 0.000131 AC: 5 AN: 38180

South Asian (SAS) AF: 0.0000359 AC: 3 AN: 83492

European-Finnish (FIN) AF: 0.000249 AC: 13 AN: 52302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5236

European-Non Finnish (NFE) AF: 0.0000328 AC: 36 AN: 1098934

Other (OTH) AF: 0.000101 AC: 6 AN: 59496

⚠️ 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: 0.000101 AC: 15 AN: 148520 Hom.: 0 Cov.: 30 AF XY: 0.000111 AC XY: 8 AN XY: 72376

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

African (AFR) AF: 0.00 AC: 0 AN: 40640

American (AMR) AF: 0.00 AC: 0 AN: 14624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.000207 AC: 1 AN: 4828

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10464

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

European-Non Finnish (NFE) AF: 0.000210 AC: 14 AN: 66798

Other (OTH) AF: 0.00 AC: 0 AN: 2026

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000674 Hom.: 0

ExAC AF: 0.000103 AC: 12

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	0.088
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		6.4
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.48		Loss of helix (P = 0.1706)
MVP		0.10
MPC		3.2
ClinPred		0.54	D
GERP RS		1.2
Varity_R		0.10
gMVP		0.70
Mutation Taster		=98/2	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: rs775301778; hg19: chr8-12042911; COSMIC: COSV58667758; COSMIC: COSV58667758;