6-170317865-G-A

Position:

• chr6-170317865-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032448.3(FAM120B):​c.475G>A​(p.Ala159Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: FAM120B NM_032448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.31

Genes affected

FAM120B (HGNC:21109): (family with sequence similarity 120 member B) Predicted to be involved in fat cell differentiation and peroxisome proliferator activated receptor signaling pathway. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM120B	NM_032448.3	c.475G>A	p.Ala159Thr	missense_variant	2/11	ENST00000476287.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM120B	ENST00000476287.4	c.475G>A	p.Ala159Thr	missense_variant	2/11	1	NM_032448.3	A2
FAM120B	ENST00000537664.5	c.544G>A	p.Ala182Thr	missense_variant	2/11	2		A2
FAM120B	ENST00000630384.2	c.511G>A	p.Ala171Thr	missense_variant	2/11	2		A2
FAM120B	ENST00000625626.1	c.-90+11023G>A		intron_variant		2		P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461890 Hom.: 0 Cov.: 35 AF XY: 0.00000825 AC XY: 6 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.475G>A (p.A159T) alteration is located in exon 2 (coding exon 1) of the FAM120B gene. This alteration results from a G to A substitution at nucleotide position 475, causing the alanine (A) at amino acid position 159 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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.99	.;.;D
Vest4		0.82
MutPred		0.50		.;.;Loss of stability (P = 0.0865);
MVP		0.74
MPC		0.71
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.31
gMVP		0.86

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: chr6-170626953;