chr8-12428730-G-T

Variant names:

• chr8-12428730-G-T
• NM_001137610.3:c.645C>A

Variant summary

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

The NM_001137610.3(FAM86B2):​c.645C>A​(p.Asn215Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.31

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08834511).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3	c.645C>A	p.Asn215Lys	missense_variant	Exon 6 of 8	ENST00000262365.9	NP_001131082.1
FAM86B2	NR_148876.2	n.431+251C>A		intron_variant	Intron 4 of 5
FAM86B2	NR_148877.2	n.350+251C>A		intron_variant	Intron 3 of 4
FAM86B2	NR_148878.2	n.631+251C>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9	c.645C>A	p.Asn215Lys	missense_variant	Exon 6 of 8	5	NM_001137610.3	ENSP00000262365.4

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000660 AC: 8 AN: 1212592 Hom.: 0 Cov.: 30 AF XY: 0.00000331 AC XY: 2 AN XY: 604464

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: 0.00000863

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.645C>A (p.N215K) 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 645, causing the asparagine (N) at amino acid position 215 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.7
DANN	Benign	0.93
DEOGEN2	Benign	0.0031	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.018
Sift	Benign	0.21	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.0	B;.
Vest4		0.082
MutPred		0.47		Gain of ubiquitination at N215 (P = 0.009);.;
MVP		0.043
MPC		2.0
ClinPred		0.038	T
GERP RS		-1.1
Varity_R		0.076
gMVP		0.31

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: chr8-12286239;