8-12183669-A-C

Variant names:

• chr8-12183669-A-C
• NM_001083537.4:c.828T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001083537.4(FAM86B1):​c.828T>G​(p.His276Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 9)
• Consequence: FAM86B1 NM_001083537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.21

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11833426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B1	NM_001083537.4	c.828T>G	p.His276Gln	missense_variant	Exon 7 of 7	ENST00000448228.7	NP_001077006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B1	ENST00000448228.7	c.828T>G	p.His276Gln	missense_variant	Exon 7 of 7	5	NM_001083537.4	ENSP00000407067.2

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 10

GnomAD4 genome Cov.: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.828T>G (p.H276Q) alteration is located in exon 7 (coding exon 7) of the FAM86B1 gene. This alteration results from a T to G substitution at nucleotide position 828, causing the histidine (H) at amino acid position 276 to be replaced by a glutamine (Q). 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	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.25
DANN	Benign	0.47
DEOGEN2	Benign	0.054	T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.80	T;T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.024
Sift	Benign	0.36	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.57	P;P
Vest4		0.15
MutPred		0.39		.;Loss of catalytic residue at D311 (P = 0.0792);
MVP		0.068
MPC		1.8
ClinPred		0.32	T
GERP RS		-2.3
Varity_R		0.097
gMVP		0.35

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-12041178;