NM_031453.4:c.607C>G

Variant names:

• chr10-14530378-G-C
• rs773674410
• NM_031453.4:c.607C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031453.4(FAM107B):​c.607C>G​(p.Arg203Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R203Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: FAM107B NM_031453.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84
• Publications: 0 publications found

Genes affected

FAM107B (HGNC:23726): (family with sequence similarity 107 member B) Predicted to act upstream of or within sensory perception of sound. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031453.4. 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
	FAM107B	NM_031453.4	MANE Select	c.607C>G	p.Arg203Gly	missense	Exon 3 of 5	NP_113641.2
	FAM107B	NM_001320741.2		c.199C>G	p.Arg67Gly	missense	Exon 2 of 4	NP_001307670.1
	FAM107B	NM_001282695.2		c.82C>G	p.Arg28Gly	missense	Exon 4 of 6	NP_001269624.1	Q9H098-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM107B	ENST00000181796.7	TSL:2 MANE Select	c.607C>G	p.Arg203Gly	missense	Exon 3 of 5	ENSP00000181796.2	Q9H098-2
	FAM107B	ENST00000378467.8	TSL:1	c.82C>G	p.Arg28Gly	missense	Exon 3 of 5	ENSP00000367728.4	Q9H098-1
	FAM107B	ENST00000378470.5	TSL:1	c.82C>G	p.Arg28Gly	missense	Exon 2 of 4	ENSP00000367731.1	Q9H098-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461654 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.015	D
Sift4G	Benign	0.073	T
Polyphen		1.0	D
Vest4		0.74
MutPred		0.58		Loss of MoRF binding (P = 0.0094)
MVP		0.60
MPC		0.63
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.60
gMVP		0.10
Mutation Taster		=22/78	disease causing

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: rs773674410; hg19: chr10-14572377;