NM_001083537.4:c.752G>T

Variant names:

• chr8-12185414-C-A
• rs376073852
• NM_001083537.4:c.752G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001083537.4(FAM86B1):​c.752G>T​(p.Arg251Leu) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R251H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B1	NM_001083537.4	c.752G>T	p.Arg251Leu	missense_variant	Exon 6 of 7	ENST00000448228.7	NP_001077006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B1	ENST00000448228.7	c.752G>T	p.Arg251Leu	missense_variant	Exon 6 of 7	5	NM_001083537.4	ENSP00000407067.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD3 exomes AF: 0.00000895 AC: 2 AN: 223436 Hom.: 0 AF XY: 0.0000164 AC XY: 2 AN XY: 121822

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000506

Gnomad NFE exome AF: 0.00000966

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000486 AC: 7 AN: 1440066 Hom.: 0 Cov.: 85 AF XY: 0.00000419 AC XY: 3 AN XY: 716168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000637

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Pathogenic	4.5	H;.
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.95	P;P
Vest4		0.81
MutPred		0.69		.;Loss of catalytic residue at R285 (P = 0.0152);
MVP		0.26
MPC		3.7
ClinPred		0.99	D
GERP RS		1.2
Varity_R		0.64
gMVP		0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs376073852; hg19: chr8-12042923;