rs1465252573

Variant names:

• chr19-38403217-G-A
• rs1465252573
• NM_174905.4:c.64G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-38403217-G-A
• chr19-38403217-G-C
• chr19-38403217-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_174905.4(FAM98C):​c.64G>A​(p.Gly22Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM98C NM_174905.4 missense, splice_region
• Scores: Splicing: ADA: 0.8168
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM98C	NM_174905.4	c.64G>A	p.Gly22Arg	missense_variant, splice_region_variant	Exon 1 of 8	ENST00000252530.10	NP_777565.3
FAM98C	NM_001351675.1	c.64G>A	p.Gly22Arg	missense_variant, splice_region_variant	Exon 1 of 6		NP_001338604.1
FAM98C	XM_017026354.2	c.64G>A	p.Gly22Arg	missense_variant, splice_region_variant	Exon 1 of 6		XP_016881843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM98C	ENST00000252530.10	c.64G>A	p.Gly22Arg	missense_variant, splice_region_variant	Exon 1 of 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: 1406646 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 699420

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

Alfa AF: 0.0000334 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Pathogenic	0.67	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.0	.;M;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.2	.;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	.;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.52
MutPred		0.86		Gain of solvent accessibility (P = 0.0055);Gain of solvent accessibility (P = 0.0055);Gain of solvent accessibility (P = 0.0055);
MVP		0.62
MPC		2.6
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.30
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.82
dbscSNV1_RF	Benign	0.61
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

LitVar

Other links and lift over

dbSNP: rs1465252573; hg19: chr19-38893857;