NM_173348.2:c.110C>T

Variant names:

• chr10-73174749-C-T
• rs1564676555
• NM_173348.2:c.110C>T

Variant summary

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

The NM_173348.2(FAM149B1):​c.110C>T​(p.Ser37Phe) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM149B1 NM_173348.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• 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: 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=0.063272804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM149B1	NM_173348.2	c.110C>T	p.Ser37Phe	missense_variant	Exon 2 of 14	ENST00000242505.11	NP_775483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM149B1	ENST00000242505.11	c.110C>T	p.Ser37Phe	missense_variant	Exon 2 of 14	5	NM_173348.2	ENSP00000242505.6

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

Apr 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.110C>T (p.S37F) alteration is located in exon 2 (coding exon 2) of the FAM149B1 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the serine (S) at amino acid position 37 to be replaced by a phenylalanine (F). 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	0.097
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.039
Sift	Benign	0.11	T
Sift4G	Uncertain	0.049	D
Polyphen		0.0090	B
Vest4		0.10
MutPred		0.17		Loss of glycosylation at S37 (P = 0.0033);
MVP		0.11
ClinPred		0.30	T
GERP RS		3.5
Varity_R		0.074
gMVP		0.13
Mutation Taster		=87/13	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: rs1564676555; hg19: chr10-74934507; COSMIC: COSV105026760; COSMIC: COSV105026760;