8-138151312-C-T

Variant names:

• chr8-138151312-C-T
• rs1467381005
• NM_015912.4:c.3163G>A

Variant summary

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

The NM_015912.4(FAM135B):​c.3163G>A​(p.Ala1055Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,132 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: FAM135B NM_015912.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02

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

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=0.09835902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM135B	NM_015912.4	c.3163G>A	p.Ala1055Thr	missense_variant	Exon 13 of 20	ENST00000395297.6	NP_056996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM135B	ENST00000395297.6	c.3163G>A	p.Ala1055Thr	missense_variant	Exon 13 of 20	5	NM_015912.4	ENSP00000378710.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74310

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3163G>A (p.A1055T) alteration is located in exon 13 (coding exon 12) of the FAM135B gene. This alteration results from a G to A substitution at nucleotide position 3163, causing the alanine (A) at amino acid position 1055 to be replaced by a threonine (T). 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	0.078
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.081
Eigen_PC	Benign	0.0099
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.064
Sift	Benign	0.075	T
Sift4G	Benign	0.44	T
Polyphen		0.68	P
Vest4		0.10
MutPred		0.13		Loss of catalytic residue at A1055 (P = 0.0219);
MVP		0.068
MPC		0.065
ClinPred		0.28	T
GERP RS		4.4
Varity_R		0.038
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs1467381005; hg19: chr8-139163555;