chr5-80522039-T-C

Variant names:

• chr5-80522039-T-C
• NM_205548.3:c.572T>C

Variant summary

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

The NM_205548.3(FAM151B):​c.572T>C​(p.Ile191Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM151B NM_205548.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28

Genes affected

FAM151B (HGNC:33716): (family with sequence similarity 151 member B) Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM151B	NM_205548.3	c.572T>C	p.Ile191Thr	missense_variant	Exon 5 of 6	ENST00000282226.5	NP_991111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM151B	ENST00000282226.5	c.572T>C	p.Ile191Thr	missense_variant	Exon 5 of 6	1	NM_205548.3	ENSP00000282226.4
FAM151B	ENST00000509292.1	n.534T>C		non_coding_transcript_exon_variant	Exon 4 of 4	3
FAM151B	ENST00000511718.5	n.1716T>C		non_coding_transcript_exon_variant	Exon 10 of 11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.572T>C (p.I191T) alteration is located in exon 5 (coding exon 5) of the FAM151B gene. This alteration results from a T to C substitution at nucleotide position 572, causing the isoleucine (I) at amino acid position 191 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	0.19
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0052	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.23
Sift	Benign	0.055	T
Sift4G	Benign	0.084	T
Polyphen		0.89	P
Vest4		0.55
MutPred		0.72		Loss of stability (P = 0.0521);
MVP		0.10
MPC		0.18
ClinPred		0.89	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr5-79817858;