NM_001079673.2:c.100-8T>C

Variant names:

• chr13-49075281-T-C
• rs111263636
• NM_001079673.2:c.100-8T>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001079673.2(FNDC3A):​c.100-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,558,272 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (33 hom.)
• Consequence: FNDC3A NM_001079673.2 splice_region, intron
• Scores: Splicing: ADA: 0.002098
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.99

Genes affected

FNDC3A (HGNC:20296): (fibronectin type III domain containing 3A) Enables RNA binding activity. Predicted to act upstream of or within several processes, including Sertoli cell development; fertilization; and spermatid development. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 13-49075281-T-C is Benign according to our data. Variant chr13-49075281-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2643814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC3A	NM_001079673.2	c.100-8T>C		splice_region_variant, intron_variant	Intron 2 of 25	ENST00000492622.6	NP_001073141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC3A	ENST00000492622.6	c.100-8T>C		splice_region_variant, intron_variant	Intron 2 of 25	1	NM_001079673.2	ENSP00000417257.1
FNDC3A	ENST00000541916.5	c.100-8T>C		splice_region_variant, intron_variant	Intron 2 of 25	1		ENSP00000441831.1
FNDC3A	ENST00000484074.5	n.100-8T>C		splice_region_variant, intron_variant	Intron 2 of 25	1		ENSP00000420275.1
FNDC3A	ENST00000378383.5	c.100-8T>C		splice_region_variant, intron_variant	Intron 2 of 7	2		ENSP00000484320.1

Frequencies

GnomAD3 genomes AF: 0.00460 AC: 700 AN: 152184 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00757

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00513 AC: 1228 AN: 239592 Hom.: 10 AF XY: 0.00532 AC XY: 692 AN XY: 130070

Gnomad AFR exome AF: 0.00119

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00837

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000921

Gnomad FIN exome AF: 0.00365

Gnomad NFE exome AF: 0.00855

Gnomad OTH exome AF: 0.00500

GnomAD4 exome AF: 0.00615 AC: 8645 AN: 1405970 Hom.: 33 Cov.: 24 AF XY: 0.00603 AC XY: 4235 AN XY: 702228

Gnomad4 AFR exome AF: 0.000908

Gnomad4 AMR exome AF: 0.00196

Gnomad4 ASJ exome AF: 0.00753

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000951

Gnomad4 FIN exome AF: 0.00454

Gnomad4 NFE exome AF: 0.00721

Gnomad4 OTH exome AF: 0.00497

GnomAD4 genome AF: 0.00460 AC: 700 AN: 152302 Hom.: 2 Cov.: 32 AF XY: 0.00434 AC XY: 323 AN XY: 74488

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00606

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.00757

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00736 Hom.: 4

Bravo AF: 0.00457

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.00560

EpiControl AF: 0.00633

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FNDC3A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.6
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.034
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: rs111263636; hg19: chr13-49649417;