19-38405574-GCCT-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM4_Supporting BP6_Moderate

The NM_174905.4(FAM98C):c.697_699del(p.Leu233del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00057 in 1,614,188 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: FAM98C NM_174905.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.75

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 Likely_benign. Variant got -1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_174905.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 19-38405574-GCCT-G is Benign according to our data. Variant chr19-38405574-GCCT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1686404.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM98C	NM_174905.4	c.697_699del	p.Leu233del	inframe_deletion	6/8	ENST00000252530.10
FAM98C	NM_001351675.1	c.619_621del	p.Leu207del	inframe_deletion	5/6
FAM98C	XM_017026354.2	c.*78_*80del		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM98C	ENST00000252530.10	c.697_699del	p.Leu233del	inframe_deletion	6/8	1	NM_174905.4	P1

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 449 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000765 AC: 191 AN: 249724 Hom.: 0 AF XY: 0.000672 AC XY: 91 AN XY: 135438

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000320 AC: 468 AN: 1461884 Hom.: 1 AF XY: 0.000268 AC XY: 195 AN XY: 727240

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.000613

GnomAD4 genome AF: 0.00297 AC: 452 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.00290 AC XY: 216 AN XY: 74472

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000588 Hom.: 0

Bravo AF: 0.00374

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs137896913; hg19: chr19-38896214;