rs201508707

Variant names:

• chr12-13055907-C-A
• rs201508707
• NM_020853.2:c.394C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-13055907-C-A
• chr12-13055907-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020853.2(FAM234B):​c.394C>A​(p.Leu132Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. L132V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM234B NM_020853.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• Publications: 0 publications found

Genes affected

FAM234B (HGNC:29288): (family with sequence similarity 234 member B) Predicted to be located in Golgi apparatus and cytoskeleton. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33029896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020853.2. 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
	FAM234B	NM_020853.2	MANE Select	c.394C>A	p.Leu132Met	missense	Exon 2 of 13	NP_065904.1	A2RU67

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM234B	ENST00000197268.13	TSL:1 MANE Select	c.394C>A	p.Leu132Met	missense	Exon 2 of 13	ENSP00000197268.8	A2RU67
	FAM234B	ENST00000893327.1		c.394C>A	p.Leu132Met	missense	Exon 2 of 12	ENSP00000563386.1
	FAM234B	ENST00000416494.6	TSL:2	n.394C>A		non_coding_transcript_exon	Exon 2 of 14	ENSP00000394063.2	A2RU67

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447154 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 718244

African (AFR) AF: 0.00 AC: 0 AN: 33140

American (AMR) AF: 0.00 AC: 0 AN: 43330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 83870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104442

Other (OTH) AF: 0.00 AC: 0 AN: 59804

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.97	T
PhyloP100		3.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.072
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.19		Gain of disorder (P = 0.1037)
MVP		0.44
MPC		0.57
ClinPred		0.90	D
GERP RS		5.3
Varity_R		0.096
gMVP		0.27
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs201508707; hg19: chr12-13208841;