8-138151576-C-T

Variant names:

• chr8-138151576-C-T
• rs2130734657
• NM_015912.4:c.2899G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015912.4(FAM135B):​c.2899G>A​(p.Ala967Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM135B NM_015912.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.817
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063593596).

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.2899G>A	p.Ala967Thr	missense	Exon 13 of 20	NP_056996.2	Q49AJ0-1
	FAM135B	NM_001362965.2		c.2899G>A	p.Ala967Thr	missense	Exon 13 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.2899G>A	p.Ala967Thr	missense	Exon 13 of 20	ENSP00000378710.1	Q49AJ0-1
	FAM135B	ENST00000467365.2	TSL:1	n.829G>A		non_coding_transcript_exon	Exon 1 of 4
	FAM135B	ENST00000482951.6	TSL:1	n.*2845G>A		non_coding_transcript_exon	Exon 14 of 21	ENSP00000429874.1	E5RH68

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461852 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.83
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.63	N
PhyloP100		-0.82
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.036
Sift	Benign	0.64	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.037
MutPred		0.20		Gain of disorder (P = 0.129)
MVP		0.043
MPC		0.063
ClinPred		0.031	T
GERP RS		0.14
Varity_R		0.030
gMVP		0.28
Mutation Taster		=100/0	polymorphism

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: rs2130734657; hg19: chr8-139163819;