chr19-38403378-T-C

Variant names:

• chr19-38403378-T-C
• NM_174905.4:c.106T>C

Variant summary

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

The NM_174905.4(FAM98C):​c.106T>C​(p.Cys36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM98C NM_174905.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.331
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.106T>C	p.Cys36Arg	missense	Exon 2 of 8	NP_777565.3
	FAM98C	NM_001351675.1		c.106T>C	p.Cys36Arg	missense	Exon 2 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.106T>C	p.Cys36Arg	missense	Exon 2 of 8	ENSP00000252530.4	Q17RN3-1
	FAM98C	ENST00000343358.11	TSL:1	c.106T>C	p.Cys36Arg	missense	Exon 2 of 6	ENSP00000340348.6	Q17RN3-2
	FAM98C	ENST00000588262.5	TSL:1	c.106T>C	p.Cys36Arg	missense	Exon 2 of 5	ENSP00000467974.1	K7EQT7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1318444 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 650998

African (AFR) AF: 0.00 AC: 0 AN: 25916

American (AMR) AF: 0.00 AC: 0 AN: 18016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22086

East Asian (EAS) AF: 0.00 AC: 0 AN: 30372

South Asian (SAS) AF: 0.00 AC: 0 AN: 70242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4952

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1057582

Other (OTH) AF: 0.00 AC: 0 AN: 54714

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.33
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.022	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.74		Gain of MoRF binding (P = 0.0026)
MVP		0.52
MPC		3.2
ClinPred		0.90	D
GERP RS		4.5
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.73
Mutation Taster		=88/12	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

hg19: chr19-38894018;