6-170317985-G-A

Variant names:

• chr6-170317985-G-A
• NM_032448.3:c.595G>A

Variant summary

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

The NM_032448.3(FAM120B):​c.595G>A​(p.Glu199Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM120B NM_032448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25

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=0.14936385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120B	NM_032448.3	c.595G>A	p.Glu199Lys	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.595G>A	p.Glu199Lys	missense_variant	Exon 2 of 11	1	NM_032448.3	ENSP00000417970.1
FAM120B	ENST00000537664.5	c.664G>A	p.Glu222Lys	missense_variant	Exon 2 of 11	2		ENSP00000440125.1
FAM120B	ENST00000630384.2	c.631G>A	p.Glu211Lys	missense_variant	Exon 2 of 11	2		ENSP00000485745.1
FAM120B	ENST00000625626.1	c.-90+11143G>A		intron_variant	Intron 1 of 8	2		ENSP00000485793.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.595G>A (p.E199K) 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 595, causing the glutamic acid (E) at amino acid position 199 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Benign	0.0088	.;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;.;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	.;N;N
REVEL	Benign	0.084
Sift	Benign	0.72	.;T;T
Sift4G	Benign	0.098	T;T;T
Polyphen		0.17	.;.;B
Vest4		0.17
MutPred		0.44		.;.;Gain of ubiquitination at E199 (P = 0.0198);
MVP		0.54
MPC		0.40
ClinPred		0.69	D
GERP RS		5.8
Varity_R		0.11
gMVP		0.42

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: chr6-170627073;