3-172399983-A-T

Variant names:

• chr3-172399983-A-T
• rs10989
• NM_022763.4:c.*2508A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022763.4(FNDC3B):​c.*2508A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 152,258 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FNDC3B NM_022763.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 1 publications found

Genes affected

FNDC3B (HGNC:24670): (fibronectin type III domain containing 3B) Enables RNA binding activity. Predicted to act upstream of or within several processes, including negative regulation of osteoblast differentiation; substrate adhesion-dependent cell spreading; and type II pneumocyte differentiation. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0118 (1801/152258) while in subpopulation AFR AF = 0.0408 (1694/41542). AF 95% confidence interval is 0.0392. There are 35 homozygotes in GnomAd4. There are 842 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1801 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022763.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3B	NM_022763.4	MANE Select	c.*2508A>T		3_prime_UTR	Exon 26 of 26	NP_073600.3
	FNDC3B	NM_001135095.2		c.*2508A>T		3_prime_UTR	Exon 26 of 26	NP_001128567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3B	ENST00000415807.7	TSL:1 MANE Select	c.*2508A>T		3_prime_UTR	Exon 26 of 26	ENSP00000411242.2
	FNDC3B	ENST00000336824.8	TSL:1	c.*2508A>T		3_prime_UTR	Exon 26 of 26	ENSP00000338523.4

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1798 AN: 152140 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0100

GnomAD4 exome Data not reliable, filtered out with message: AC0;InbreedingCoeff AF: 0.00 AC: 0 AN: 434 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0118 AC: 1801 AN: 152258 Hom.: 35 Cov.: 33 AF XY: 0.0113 AC XY: 842 AN XY: 74446

African (AFR) AF: 0.0408 AC: 1694 AN: 41542

American (AMR) AF: 0.00333 AC: 51 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68008

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.0138

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.76
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10989; hg19: chr3-172117773;