19-38403378-T-C

Position:

• chr19-38403378-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

FAM98C (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM98C	NM_174905.4	c.106T>C	p.Cys36Arg	missense_variant	2/8	ENST00000252530.10	NP_777565.3
FAM98C	NM_001351675.1	c.106T>C	p.Cys36Arg	missense_variant	2/6		NP_001338604.1
FAM98C	XM_017026354.2	c.106T>C	p.Cys36Arg	missense_variant	2/6		XP_016881843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM98C	ENST00000252530.10	c.106T>C	p.Cys36Arg	missense_variant	2/8	1	NM_174905.4	ENSP00000252530.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.106T>C (p.C36R) alteration is located in exon 2 (coding exon 2) of the FAM98C gene. This alteration results from a T to C substitution at nucleotide position 106, causing the cysteine (C) at amino acid position 36 to be replaced by an arginine (R). 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	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;T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.8	.;M;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	.;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.022	.;D;D
Sift4G	Pathogenic	0.0	D;T;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.62
MutPred		0.74		Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);
MVP		0.52
MPC		3.2
ClinPred		0.90	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-38894018;