chr6-170318274-C-T

Variant names:

• chr6-170318274-C-T
• NM_032448.3:c.884C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032448.3(FAM120B):​c.884C>T​(p.Ala295Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM120B NM_032448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22690365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032448.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120B	NM_032448.3	MANE Select	c.884C>T	p.Ala295Val	missense	Exon 2 of 11	NP_115824.1	Q96EK7-1
	FAM120B	NM_001286380.2		c.953C>T	p.Ala318Val	missense	Exon 2 of 11	NP_001273309.1	F5GY05
	FAM120B	NM_001286379.2		c.920C>T	p.Ala307Val	missense	Exon 2 of 11	NP_001273308.1	A0A0D9SEJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120B	ENST00000476287.4	TSL:1 MANE Select	c.884C>T	p.Ala295Val	missense	Exon 2 of 11	ENSP00000417970.1	Q96EK7-1
	FAM120B	ENST00000537664.5	TSL:2	c.953C>T	p.Ala318Val	missense	Exon 2 of 11	ENSP00000440125.1	F5GY05
	FAM120B	ENST00000630384.2	TSL:2	c.920C>T	p.Ala307Val	missense	Exon 2 of 11	ENSP00000485745.1	A0A0D9SEJ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461748 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727162

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0075	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.12
Sift	Benign	0.13	T
Sift4G	Benign	0.10	T
Polyphen		0.98	D
Vest4		0.23
MutPred		0.41		Gain of methylation at K294 (P = 0.0354)
MVP		0.54
MPC		0.57
ClinPred		0.87	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.22
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr6-170627362;