6-170318457-G-T

Variant summary

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

The NM_032448.3(FAM120B):c.1067G>T(p.Cys356Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM120B NM_032448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.611

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10263455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM120B	NM_032448.3	c.1067G>T	p.Cys356Phe	missense_variant	2/11	ENST00000476287.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM120B	ENST00000476287.4	c.1067G>T	p.Cys356Phe	missense_variant	2/11	1	NM_032448.3	A2
FAM120B	ENST00000537664.5	c.1136G>T	p.Cys379Phe	missense_variant	2/11	2		A2
FAM120B	ENST00000630384.2	c.1103G>T	p.Cys368Phe	missense_variant	2/11	2		A2
FAM120B	ENST00000625626.1	c.-90+11615G>T		intron_variant		2		P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453244 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 722866

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

Jun 22, 2021

The c.1067G>T (p.C356F) alteration is located in exon 2 (coding exon 1) of the FAM120B gene. This alteration results from a G to T substitution at nucleotide position 1067, causing the cysteine (C) at amino acid position 356 to be replaced by a phenylalanine (F). 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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	17
Dann	Benign	0.97
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.082	T;T;T
Polyphen		0.22	.;.;B
Vest4		0.26
MutPred		0.14		.;.;Gain of phosphorylation at T357 (P = 0.2449);
MVP		0.33
MPC		0.36
ClinPred		0.070	T
GERP RS		0.95
Varity_R		0.068
gMVP		0.14

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: rs995191901; hg19: chr6-170627545;