8-12428654-G-T

Variant names:

• chr8-12428654-G-T
• NM_001137610.3:c.721C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001137610.3(FAM86B2):​c.721C>A​(p.Pro241Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

Genes affected

FAM86B2 (HGNC:32222): (family with sequence similarity 86 member B2) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4008226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3	c.721C>A	p.Pro241Thr	missense_variant	Exon 6 of 8	ENST00000262365.9	NP_001131082.1
FAM86B2	NR_148876.2	n.431+327C>A		intron_variant	Intron 4 of 5
FAM86B2	NR_148877.2	n.350+327C>A		intron_variant	Intron 3 of 4
FAM86B2	NR_148878.2	n.631+327C>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9	c.721C>A	p.Pro241Thr	missense_variant	Exon 6 of 8	5	NM_001137610.3	ENSP00000262365.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.721C>A (p.P241T) alteration is located in exon 6 (coding exon 6) of the FAM86B2 gene. This alteration results from a C to A substitution at nucleotide position 721, causing the proline (P) at amino acid position 241 to be replaced by a threonine (T). 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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Benign	0.074
Sift	Benign	0.30	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.37	B;.
Vest4		0.41
MutPred		0.69		Loss of stability (P = 0.126);.;
MVP		0.068
MPC		3.0
ClinPred		0.67	D
GERP RS		1.2
Varity_R		0.14
gMVP		0.48

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: chr8-12286163;