6-170317608-A-G

Variant names:

• chr6-170317608-A-G
• NM_032448.3:c.218A>G

Variant summary

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

The NM_032448.3(FAM120B):​c.218A>G​(p.Asp73Gly) 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. 16/21 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)
• 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=0.101192355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120B	NM_032448.3	c.218A>G	p.Asp73Gly	missense_variant	Exon 2 of 11	ENST00000476287.4	NP_115824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM120B	ENST00000476287.4	c.218A>G	p.Asp73Gly	missense_variant	Exon 2 of 11	1	NM_032448.3	ENSP00000417970.1
FAM120B	ENST00000537664.5	c.287A>G	p.Asp96Gly	missense_variant	Exon 2 of 11	2		ENSP00000440125.1
FAM120B	ENST00000630384.2	c.254A>G	p.Asp85Gly	missense_variant	Exon 2 of 11	2		ENSP00000485745.1
FAM120B	ENST00000625626.1	c.-90+10766A>G		intron_variant	Intron 1 of 8	2		ENSP00000485793.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.218A>G (p.D73G) alteration is located in exon 2 (coding exon 1) of the FAM120B gene. This alteration results from a A to G substitution at nucleotide position 218, causing the aspartic acid (D) at amino acid position 73 to be replaced by a glycine (G). 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	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.031	.;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;.;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	.;N;N
REVEL	Benign	0.035
Sift	Benign	0.34	.;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.015	.;.;B
Vest4		0.16
MutPred		0.44		.;.;Loss of stability (P = 0.0089);
MVP		0.45
MPC		0.24
ClinPred		0.048	T
GERP RS		3.6
Varity_R		0.076
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-170626696;