19-38403667-G-C

Variant names:

• chr19-38403667-G-C
• rs150024474
• NM_174905.4:c.322G>C

Variant summary

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

The NM_174905.4(FAM98C):​c.322G>C​(p.Glu108Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000495 in 1,415,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. E108K) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: FAM98C NM_174905.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 5 publications found

Genes affected

FAM98C (HGNC:27119): (family with sequence similarity 98 member C) Predicted to be part of tRNA-splicing ligase complex. [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=0.07222888).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174905.4. 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
	FAM98C	NM_174905.4	MANE Select	c.322G>C	p.Glu108Gln	missense	Exon 3 of 8	NP_777565.3
	FAM98C	NM_001351675.1		c.322G>C	p.Glu108Gln	missense	Exon 3 of 6	NP_001338604.1	Q17RN3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM98C	ENST00000252530.10	TSL:1 MANE Select	c.322G>C	p.Glu108Gln	missense	Exon 3 of 8	ENSP00000252530.4	Q17RN3-1
	FAM98C	ENST00000343358.11	TSL:1	c.322G>C	p.Glu108Gln	missense	Exon 3 of 6	ENSP00000340348.6	Q17RN3-2
	FAM98C	ENST00000588262.5	TSL:1	c.322G>C	p.Glu108Gln	missense	Exon 3 of 5	ENSP00000467974.1	K7EQT7

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000230 AC: 1 AN: 43402 AF XY: 0.0000393

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000704

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: 0.00000238 AC: 3 AN: 1262760 Hom.: 0 Cov.: 32 AF XY: 0.00000325 AC XY: 2 AN XY: 615878

African (AFR) AF: 0.00 AC: 0 AN: 25224

American (AMR) AF: 0.00 AC: 0 AN: 16138

Ashkenazi Jewish (ASJ) AF: 0.000108 AC: 2 AN: 18528

East Asian (EAS) AF: 0.00 AC: 0 AN: 28622

South Asian (SAS) AF: 0.00 AC: 0 AN: 60548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3836

European-Non Finnish (NFE) AF: 9.74e-7 AC: 1 AN: 1026406

Other (OTH) AF: 0.00 AC: 0 AN: 52180

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74462

African (AFR) AF: 0.0000722 AC: 3 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 219

Bravo AF: 0.0000340

ExAC AF: 0.00000902 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.5
DANN	Benign	0.79
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.0040
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.025
Sift	Benign	0.46	T
Sift4G	Benign	0.066	T
Polyphen		0.64	P
Vest4		0.081
MutPred		0.29		Gain of MoRF binding (P = 0.09)
MVP		0.25
MPC		1.8
ClinPred		0.050	T
GERP RS		0.29
PromoterAI		0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.066
gMVP		0.21
Mutation Taster		=100/0	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: rs150024474; hg19: chr19-38894307;