6-159225301-T-C

Variant names:

• chr6-159225301-T-C
• rs365302
• NM_032532.3:c.885-234T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032532.3(FNDC1):​c.885-234T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,524 control chromosomes in the GnomAD database, including 14,139 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 0.38 (14139 hom., cov: 31)
• Consequence: FNDC1 NM_032532.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 14 publications found

Genes affected

FNDC1 (HGNC:21184): (fibronectin type III domain containing 1) Predicted to act upstream of or within several processes, including cellular response to hypoxia; positive regulation of cardiac muscle cell apoptotic process; and positive regulation of protein phosphorylation. Located in nuclear speck. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032532.3. 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
	FNDC1	NM_032532.3	MANE Select	c.885-234T>C		intron	N/A	NP_115921.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC1	ENST00000297267.14	TSL:1 MANE Select	c.885-234T>C		intron	N/A	ENSP00000297267.9
	FNDC1	ENST00000329629.8	TSL:1	c.759-234T>C		intron	N/A	ENSP00000333297.8
	FNDC1	ENST00000480856.1	TSL:3	n.520-234T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57833 AN: 151408 Hom.: 14093 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.333

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.382 AC: 57938 AN: 151524 Hom.: 14139 Cov.: 31 AF XY: 0.385 AC XY: 28491 AN XY: 74008

African (AFR) AF: 0.666 AC: 27451 AN: 41192

American (AMR) AF: 0.303 AC: 4610 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3693 AN: 5084

South Asian (SAS) AF: 0.404 AC: 1943 AN: 4808

European-Finnish (FIN) AF: 0.244 AC: 2562 AN: 10506

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.235 AC: 15943 AN: 67936

Other (OTH) AF: 0.338 AC: 713 AN: 2108

Alfa AF: 0.291 Hom.: 7492

Bravo AF: 0.403

Asia WGS AF: 0.553 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.1
DANN	Benign	0.78
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs365302; hg19: chr6-159646333;