1-121183354-C-T

Variant names:

• chr1-121183354-C-T
• NM_001100910.2:c.136G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001100910.2(FAM72B):​c.136G>A​(p.Asp46Asn) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 11)
• Consequence: FAM72B NM_001100910.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.99

Genes affected

FAM72B (HGNC:24805): (family with sequence similarity 72 member B) Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72B	NM_001100910.2	c.136G>A	p.Asp46Asn	missense_variant	Exon 1 of 4	ENST00000369390.7	NP_001094380.1
FAM72B	NM_001320149.2	c.32+104G>A		intron_variant	Intron 1 of 3		NP_001307078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72B	ENST00000369390.7	c.136G>A	p.Asp46Asn	missense_variant	Exon 1 of 4	1	NM_001100910.2	ENSP00000358397.3

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Cov.: 17

GnomAD4 genome Cov.: 11

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.136G>A (p.D46N) alteration is located in exon 1 (coding exon 1) of the FAM72B gene. This alteration results from a G to A substitution at nucleotide position 136, causing the aspartic acid (D) at amino acid position 46 to be replaced by an asparagine (N). 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	Pathogenic	0.89
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	34
DEOGEN2	Benign	0.12	T;.;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Benign	-0.52	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.1	D;.;D
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.80
MutPred		0.69		Loss of glycosylation at S44 (P = 0.1392);Loss of glycosylation at S44 (P = 0.1392);.;
MVP		0.59
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.71
gMVP		0.70

Splicing

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: chr1-143912160;