6-170317565-A-G

Variant names:

• chr6-170317565-A-G
• NM_032448.3:c.175A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032448.3(FAM120B):​c.175A>G​(p.Ile59Val) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM120B NM_032448.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.36

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05184588).
• BP6: Variant 6-170317565-A-G is Benign according to our data. Variant chr6-170317565-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3511585.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120B	NM_032448.3	c.175A>G	p.Ile59Val	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.175A>G	p.Ile59Val	missense_variant	Exon 2 of 11	1	NM_032448.3	ENSP00000417970.1
FAM120B	ENST00000537664.5	c.244A>G	p.Ile82Val	missense_variant	Exon 2 of 11	2		ENSP00000440125.1
FAM120B	ENST00000630384.2	c.211A>G	p.Ile71Val	missense_variant	Exon 2 of 11	2		ENSP00000485745.1
FAM120B	ENST00000625626.1	c.-90+10723A>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: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 29, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.4
DANN	Benign	0.41
DEOGEN2	Benign	0.0080	.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.98	.;.;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.39	.;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	.;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.021	.;.;B
Vest4		0.021
MutPred		0.30		.;.;Gain of relative solvent accessibility (P = 0.1571);
MVP		0.35
MPC		0.15
ClinPred		0.041	T
GERP RS		-6.1
Varity_R		0.032
gMVP		0.36

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: chr6-170626653;