rs763793043

Variant names:

• chr8-12185408-G-A
• rs763793043
• NM_001083537.4:c.758C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-12185408-G-A
• chr8-12185408-G-C
• chr8-12185408-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001083537.4(FAM86B1):​c.758C>T​(p.Pro253Leu) 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. 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. P253R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21362776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B1	NM_001083537.4	c.758C>T	p.Pro253Leu	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.758C>T	p.Pro253Leu	missense_variant	Exon 6 of 7	5	NM_001083537.4	ENSP00000407067.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000875 AC: 2 AN: 228478 Hom.: 0 AF XY: 0.0000161 AC XY: 2 AN XY: 124548

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000950

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000417 AC: 6 AN: 1440176 Hom.: 0 Cov.: 97 AF XY: 0.00000558 AC XY: 4 AN XY: 716226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000230

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: 0.00000364

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000173 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.86	D;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Benign	0.14
Sift	Benign	0.098	T;T
Sift4G	Uncertain	0.058	T;T
Polyphen		0.028	B;B
Vest4		0.40
MutPred		0.47		.;Gain of stability (P = 0.1765);
MVP		0.11
MPC		1.9
ClinPred		0.26	T
GERP RS		1.2
Varity_R		0.13
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

LitVar

Other links and lift over

dbSNP: rs763793043; hg19: chr8-12042917;