8-12185414-C-T

Variant names:

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

Variant summary

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

The NM_001083537.4(FAM86B1):​c.752G>A​(p.Arg251His) variant causes a missense change. The variant allele was found at a frequency of 0.000148 in 148,376 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00011 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B1	NM_001083537.4	c.752G>A	p.Arg251His	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>A	p.Arg251His	missense_variant	Exon 6 of 7	5	NM_001083537.4	ENSP00000407067.2

Frequencies

GnomAD3 genomes AF: 0.000155 AC: 23 AN: 148262 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000208

Gnomad SAS AF: 0.000222

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000240

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000148 AC: 33 AN: 223436 Hom.: 3 AF XY: 0.000156 AC XY: 19 AN XY: 121822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000373

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.000180

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000110 AC: 159 AN: 1439914 Hom.: 9 Cov.: 85 AF XY: 0.000141 AC XY: 101 AN XY: 716084

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.0000230

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000786

Gnomad4 SAS exome AF: 0.000467

Gnomad4 FIN exome AF: 0.0000383

Gnomad4 NFE exome AF: 0.0000892

Gnomad4 OTH exome AF: 0.000151

GnomAD4 genome AF: 0.000148 AC: 22 AN: 148376 Hom.: 0 Cov.: 28 AF XY: 0.000207 AC XY: 15 AN XY: 72384

Gnomad4 AFR AF: 0.0000738

Gnomad4 AMR AF: 0.000137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000209

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000240

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000159 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000193 AC: 1

ExAC AF: 0.000216 AC: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.752G>A (p.R251H) alteration is located in exon 6 (coding exon 6) of the FAM86B1 gene. This alteration results from a G to A substitution at nucleotide position 752, causing the arginine (R) at amino acid position 251 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.1	M;.
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.16
Sift	Benign	0.050	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.49	P;B
Vest4		0.73
MVP		0.10
MPC		3.4
ClinPred		0.49	T
GERP RS		1.2
Varity_R		0.12
gMVP		0.74

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; COSMIC: COSV58670461; COSMIC: COSV58670461;