chr19-38403209-T-C

Position:

• chr19-38403209-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_174905.4(FAM98C):​c.56T>C​(p.Leu19Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • 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: -2.55

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2871906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM98C	NM_174905.4	c.56T>C	p.Leu19Pro	missense_variant	1/8	ENST00000252530.10	NP_777565.3
FAM98C	NM_001351675.1	c.56T>C	p.Leu19Pro	missense_variant	1/6		NP_001338604.1
FAM98C	XM_017026354.2	c.56T>C	p.Leu19Pro	missense_variant	1/6		XP_016881843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM98C	ENST00000252530.10	c.56T>C	p.Leu19Pro	missense_variant	1/8	1	NM_174905.4	ENSP00000252530.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1406624 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 699702

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.: 32

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

Nov 13, 2024

The c.56T>C (p.L19P) alteration is located in exon 1 (coding exon 1) of the FAM98C gene. This alteration results from a T to C substitution at nucleotide position 56, causing the leucine (L) at amino acid position 19 to be replaced by a proline (P). 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	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.2
DANN	Benign	0.85
DEOGEN2	Benign	0.031	T;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	.;L;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.15	.;N;N
REVEL	Benign	0.17
Sift	Benign	0.059	.;T;T
Sift4G	Uncertain	0.018	D;T;T
Polyphen		0.86, 0.83	.;P;P
Vest4		0.24
MutPred		0.53		Loss of stability (P = 0.0044);Loss of stability (P = 0.0044);Loss of stability (P = 0.0044);
MVP		0.53
MPC		2.8
ClinPred		0.55	D
GERP RS		-6.4
Varity_R		0.12
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-38893849;