NM_001083537.4:c.760G>C

Variant names:

• chr8-12185406-C-G
• rs368239132
• NM_001083537.4:c.760G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001083537.4(FAM86B1):​c.760G>C​(p.Glu254Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 148,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000015 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12739661).

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.760G>C	p.Glu254Gln	missense	Exon 6 of 7	NP_001077006.1	Q8N7N1-2
	FAM86B1	NR_003494.3		n.557G>C		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.760G>C	p.Glu254Gln	missense	Exon 6 of 7	ENSP00000407067.2	Q8N7N1-2
	FAM86B1	ENST00000524893.5	TSL:1	n.*310G>C		non_coding_transcript_exon	Exon 4 of 5	ENSP00000436024.1	E9PLW5
	FAM86B1	ENST00000524893.5	TSL:1	n.*310G>C		3_prime_UTR	Exon 4 of 5	ENSP00000436024.1	E9PLW5

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 4 AN: 148558 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000599

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000172 AC: 4 AN: 232874 AF XY: 0.0000157

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: 0.0000374

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000153 AC: 22 AN: 1440172 Hom.: 1 Cov.: 94 AF XY: 0.0000154 AC XY: 11 AN XY: 716222

⚠️ 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: 33240

American (AMR) AF: 0.00 AC: 0 AN: 43436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 38180

South Asian (SAS) AF: 0.00 AC: 0 AN: 83494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52288

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

European-Non Finnish (NFE) AF: 0.0000200 AC: 22 AN: 1098944

Other (OTH) AF: 0.00 AC: 0 AN: 59498

⚠️ 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 AF: 0.0000269 AC: 4 AN: 148558 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 1 AN XY: 72404

⚠️ 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: 40652

American (AMR) AF: 0.00 AC: 0 AN: 14636

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4826

South Asian (SAS) AF: 0.00 AC: 0 AN: 4522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10466

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

European-Non Finnish (NFE) AF: 0.0000599 AC: 4 AN: 66820

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 = 0.0000521060), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000482 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000192 AC: 1

ExAC AF: 0.0000172 AC: 2

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	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.3
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.013
Sift	Benign	0.16	T
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.23
MVP		0.043
MPC		2.2
ClinPred		0.044	T
GERP RS		0.16
Varity_R		0.072
gMVP		0.31
Mutation Taster		=98/2	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: rs368239132; hg19: chr8-12042915;