NM_205548.3:c.77C>A

Variant names:

• chr5-80501843-C-A
• rs372187543
• NM_205548.3:c.77C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_205548.3(FAM151B):​c.77C>A​(p.Thr26Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. T26I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM151B NM_205548.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082264334).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205548.3. 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
	FAM151B	NM_205548.3	MANE Select	c.77C>A	p.Thr26Lys	missense	Exon 2 of 6	NP_991111.2	Q6UXP7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM151B	ENST00000282226.5	TSL:1 MANE Select	c.77C>A	p.Thr26Lys	missense	Exon 2 of 6	ENSP00000282226.4	Q6UXP7
	FAM151B	ENST00000869019.1		c.26-11761C>A		intron	N/A	ENSP00000539078.1
	FAM151B	ENST00000502608.5	TSL:3	n.77C>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000427035.1	D6RD51

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247664 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451406 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722314

African (AFR) AF: 0.00 AC: 0 AN: 33226

American (AMR) AF: 0.00 AC: 0 AN: 43994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.00 AC: 0 AN: 39338

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105436

Other (OTH) AF: 0.00 AC: 0 AN: 59856

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		2.5
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.048
Sift	Benign	0.62	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.34		Gain of ubiquitination at T26 (P = 0.0155)
MVP		0.040
MPC		0.12
ClinPred		0.29	T
GERP RS		5.0
Varity_R		0.098
gMVP		0.37
Mutation Taster		=83/17	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: rs372187543; hg19: chr5-79797662;