rs781131842

Variant names:

• chr10-73177859-A-C
• rs781131842
• NM_173348.2:c.166A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-73177859-A-C
• chr10-73177859-A-G

Variant summary

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

The NM_173348.2(FAM149B1):​c.166A>C​(p.Thr56Pro) 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. 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. T56A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM149B1 NM_173348.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 0 publications found

Genes affected

FAM149B1 (HGNC:29162): (family with sequence similarity 149 member B1) Involved in cilium assembly and protein localization to cilium. Predicted to be located in cilium. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Apr 2022]

FAM149B1 Gene-Disease associations (from GenCC):

• Joubert syndrome 36

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=0.13956022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM149B1	NM_173348.2	c.166A>C	p.Thr56Pro	missense_variant	Exon 3 of 14	ENST00000242505.11	NP_775483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM149B1	ENST00000242505.11	c.166A>C	p.Thr56Pro	missense_variant	Exon 3 of 14	5	NM_173348.2	ENSP00000242505.6
FAM149B1	ENST00000372955.7	c.-15A>C		upstream_gene_variant		1		ENSP00000362046.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0048	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.12
Sift	Uncertain	0.020	D
Sift4G	Benign	0.16	T
Polyphen		0.88	P
Vest4		0.13
MutPred		0.099		Loss of phosphorylation at T56 (P = 0.0173);
MVP		0.055
ClinPred		0.65	D
GERP RS		5.3
PromoterAI		-0.083	Neutral
Varity_R		0.24
gMVP		0.21
Mutation Taster		=68/32	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: rs781131842; hg19: chr10-74937617;