rs1277017

Positions:

• chr1-108733446-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144937.3(FNDC7):​c.2054C>T​(p.Pro685Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,613,942 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P685T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.024 (143 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (158 hom.)
• Consequence: FNDC7 NM_001144937.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

Genes affected

FNDC7 (HGNC:26668): (fibronectin type III domain containing 7) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024515688).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC7	NM_001144937.3	c.2054C>T	p.Pro685Leu	missense_variant	10/13	ENST00000370017.9	NP_001138409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC7	ENST00000370017.9	c.2054C>T	p.Pro685Leu	missense_variant	10/13	5	NM_001144937.3	ENSP00000359034.3
FNDC7	ENST00000445274.1	c.1379C>T	p.Pro460Leu	missense_variant	6/8	1		ENSP00000405986.1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3605 AN: 151960 Hom.: 143 Cov.: 31

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00904

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00618 AC: 1549 AN: 250616 Hom.: 63 AF XY: 0.00441 AC XY: 598 AN XY: 135566

Gnomad AFR exome AF: 0.0829

Gnomad AMR exome AF: 0.00422

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00261 AC: 3822 AN: 1461864 Hom.: 158 Cov.: 32 AF XY: 0.00224 AC XY: 1631 AN XY: 727236

Gnomad4 AFR exome AF: 0.0879

Gnomad4 AMR exome AF: 0.00501

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000185

Gnomad4 OTH exome AF: 0.00614

GnomAD4 genome AF: 0.0237 AC: 3607 AN: 152078 Hom.: 143 Cov.: 31 AF XY: 0.0231 AC XY: 1721 AN XY: 74350

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.00903

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00494 Hom.: 55

Bravo AF: 0.0268

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0785 AC: 346

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00762 AC: 925

Asia WGS AF: 0.00722 AC: 26 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Benign	0.66
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.077
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0025	T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.46
Sift	Benign	0.90	T
Sift4G	Benign	1.0	T
Vest4		0.23
MVP		0.80
MPC		0.14
ClinPred		0.019	T
GERP RS		4.9
Varity_R		0.11
gMVP		0.31

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: rs1277017; hg19: chr1-109276068;