8-138148544-C-G

Variant names:

• chr8-138148544-C-G
• rs35765793
• NM_015912.4:c.3424G>C

Variant summary

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

The NM_015912.4(FAM135B):​c.3424G>C​(p.Val1142Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1142I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM135B NM_015912.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.12
• Publications: 0 publications found

Genes affected

FAM135B (HGNC:28029): (family with sequence similarity 135 member B) Predicted to be involved in cellular lipid metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015912.4. 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
	FAM135B	NM_015912.4	MANE Select	c.3424G>C	p.Val1142Leu	missense	Exon 14 of 20	NP_056996.2	Q49AJ0-1
	FAM135B	NM_001362965.2		c.3424G>C	p.Val1142Leu	missense	Exon 14 of 20	NP_001349894.1	Q49AJ0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM135B	ENST00000395297.6	TSL:5 MANE Select	c.3424G>C	p.Val1142Leu	missense	Exon 14 of 20	ENSP00000378710.1	Q49AJ0-1
	FAM135B	ENST00000467365.2	TSL:1	n.1250G>C		non_coding_transcript_exon	Exon 2 of 4
	FAM135B	ENST00000482951.6	TSL:1	n.*3370G>C		non_coding_transcript_exon	Exon 15 of 21	ENSP00000429874.1	E5RH68

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.63		Gain of catalytic residue at V1142 (P = 0.0497)
MVP		0.16
MPC		2.0
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.48
gMVP		0.82
Mutation Taster		=46/54	disease causing

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

dbSNP: rs35765793; hg19: chr8-139160787;