5-80488134-C-A

Variant names:

• chr5-80488134-C-A
• rs1018746636
• NM_205548.3:c.11C>A

Variant summary

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

The NM_205548.3(FAM151B):​c.11C>A​(p.Ser4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S4C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM151B NM_205548.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• 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]

FAM151B-DT (HGNC:55578): (FAM151B divergent transcript)

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=0.05830738).

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.11C>A	p.Ser4Tyr	missense	Exon 1 of 6	NP_991111.2	Q6UXP7
	FAM151B-DT	NR_172938.1		n.-188G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM151B	ENST00000282226.5	TSL:1 MANE Select	c.11C>A	p.Ser4Tyr	missense	Exon 1 of 6	ENSP00000282226.4	Q6UXP7
	FAM151B	ENST00000869019.1		c.11C>A	p.Ser4Tyr	missense	Exon 1 of 5	ENSP00000539078.1
	FAM151B	ENST00000502608.5	TSL:3	n.11C>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000427035.1	D6RD51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1390934 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 686582

African (AFR) AF: 0.00 AC: 0 AN: 31214

American (AMR) AF: 0.00 AC: 0 AN: 36004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25084

East Asian (EAS) AF: 0.00 AC: 0 AN: 35654

South Asian (SAS) AF: 0.00 AC: 0 AN: 79124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079450

Other (OTH) AF: 0.00 AC: 0 AN: 57864

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.14
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.0080
Sift	Benign	0.085	T
Sift4G	Benign	0.12	T
Polyphen		0.044	B
Vest4		0.21
MutPred		0.25		Loss of glycosylation at S4 (P = 0.0053)
MVP		0.030
MPC		0.13
ClinPred		0.12	T
GERP RS		-0.060
PromoterAI		0.045	Neutral
Varity_R		0.049
gMVP		0.42
Mutation Taster		=99/1	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: rs1018746636; hg19: chr5-79783953;